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2009
Cruz J A, Westhof E
The dynamic landscapes of RNA architecture Journal Article
In: Cell, vol. 136, no. 4, pp. 604-609, 2009, ISSN: 1097-4172 (Electronic) 0092-8674 (Linking), (Cruz, Jose Almeida Westhof, Eric Research Support, Non-U.S. Gov't United States Cell Cell. 2009 Feb 20;136(4):604-9.).
Abstract | Links | BibTeX | Tags: Animals Base Sequence Humans Models, Molecular Molecular Sequence Data Nucleic Acid Conformation RNA/*chemistry Thermodynamics, Unité ARN, WESTHOF
@article{,
title = {The dynamic landscapes of RNA architecture},
author = {J A Cruz and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19239882},
doi = {S0092-8674(09)00139-1 [pii] 10.1016/j.cell.2009.02.003},
issn = {1097-4172 (Electronic) 0092-8674 (Linking)},
year = {2009},
date = {2009-01-01},
journal = {Cell},
volume = {136},
number = {4},
pages = {604-609},
abstract = {A wealth of information on RNA folding and ribonucleoprotein assembly has emerged from analyses of structures and from the use of innovative biophysical tools. Although integrating data obtained from static structures with dynamic measurements presents major challenges, such efforts are opening new vistas on the RNA folding landscape.},
note = {Cruz, Jose Almeida
Westhof, Eric
Research Support, Non-U.S. Gov't
United States
Cell
Cell. 2009 Feb 20;136(4):604-9.},
keywords = {Animals Base Sequence Humans Models, Molecular Molecular Sequence Data Nucleic Acid Conformation RNA/*chemistry Thermodynamics, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
A wealth of information on RNA folding and ribonucleoprotein assembly has emerged from analyses of structures and from the use of innovative biophysical tools. Although integrating data obtained from static structures with dynamic measurements presents major challenges, such efforts are opening new vistas on the RNA folding landscape.
Brown J W, Birmingham A, Griffiths P E, Jossinet F, Kachouri-Lafond R, Knight R, Lang B F, Leontis N, Steger G, Stombaugh J, Westhof E
The RNA structure alignment ontology Journal Article
In: RNA, vol. 15, no. 9, pp. 1623-1631, 2009, ISSN: 1469-9001 (Electronic) 1355-8382 (Linking), (Brown, James W Birmingham, Amanda Griffiths, Paul E Jossinet, Fabrice Kachouri-Lafond, Rym Knight, Rob Lang, B Franz Leontis, Neocles Steger, Gerhard Stombaugh, Jesse Westhof, Eric Letter Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States RNA (New York, N.Y.) RNA. 2009 Sep;15(9):1623-31. Epub 2009 Jul 21.).
Abstract | Links | BibTeX | Tags: Animals Base Sequence Humans Models, Biological Molecular Sequence Data Nucleic Acid Conformation Phylogeny RNA/*analysis/chemistry Sequence Alignment/*methods/trends Sequence Analysis, Nucleic Acid *Software, RNA/methods Sequence Homology, Unité ARN, WESTHOF
@article{,
title = {The RNA structure alignment ontology},
author = {J W Brown and A Birmingham and P E Griffiths and F Jossinet and R Kachouri-Lafond and R Knight and B F Lang and N Leontis and G Steger and J Stombaugh and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19622678},
doi = {rna.1601409 [pii] 10.1261/rna.1601409},
issn = {1469-9001 (Electronic) 1355-8382 (Linking)},
year = {2009},
date = {2009-01-01},
journal = {RNA},
volume = {15},
number = {9},
pages = {1623-1631},
abstract = {Multiple sequence alignments are powerful tools for understanding the structures, functions, and evolutionary histories of linear biological macromolecules (DNA, RNA, and proteins), and for finding homologs in sequence databases. We address several ontological issues related to RNA sequence alignments that are informed by structure. Multiple sequence alignments are usually shown as two-dimensional (2D) matrices, with rows representing individual sequences, and columns identifying nucleotides from different sequences that correspond structurally, functionally, and/or evolutionarily. However, the requirement that sequences and structures correspond nucleotide-by-nucleotide is unrealistic and hinders representation of important biological relationships. High-throughput sequencing efforts are also rapidly making 2D alignments unmanageable because of vertical and horizontal expansion as more sequences are added. Solving the shortcomings of traditional RNA sequence alignments requires explicit annotation of the meaning of each relationship within the alignment. We introduce the notion of "correspondence," which is an equivalence relation between RNA elements in sets of sequences as the basis of an RNA alignment ontology. The purpose of this ontology is twofold: first, to enable the development of new representations of RNA data and of software tools that resolve the expansion problems with current RNA sequence alignments, and second, to facilitate the integration of sequence data with secondary and three-dimensional structural information, as well as other experimental information, to create simultaneously more accurate and more exploitable RNA alignments.},
note = {Brown, James W
Birmingham, Amanda
Griffiths, Paul E
Jossinet, Fabrice
Kachouri-Lafond, Rym
Knight, Rob
Lang, B Franz
Leontis, Neocles
Steger, Gerhard
Stombaugh, Jesse
Westhof, Eric
Letter
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
United States
RNA (New York, N.Y.)
RNA. 2009 Sep;15(9):1623-31. Epub 2009 Jul 21.},
keywords = {Animals Base Sequence Humans Models, Biological Molecular Sequence Data Nucleic Acid Conformation Phylogeny RNA/*analysis/chemistry Sequence Alignment/*methods/trends Sequence Analysis, Nucleic Acid *Software, RNA/methods Sequence Homology, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Multiple sequence alignments are powerful tools for understanding the structures, functions, and evolutionary histories of linear biological macromolecules (DNA, RNA, and proteins), and for finding homologs in sequence databases. We address several ontological issues related to RNA sequence alignments that are informed by structure. Multiple sequence alignments are usually shown as two-dimensional (2D) matrices, with rows representing individual sequences, and columns identifying nucleotides from different sequences that correspond structurally, functionally, and/or evolutionarily. However, the requirement that sequences and structures correspond nucleotide-by-nucleotide is unrealistic and hinders representation of important biological relationships. High-throughput sequencing efforts are also rapidly making 2D alignments unmanageable because of vertical and horizontal expansion as more sequences are added. Solving the shortcomings of traditional RNA sequence alignments requires explicit annotation of the meaning of each relationship within the alignment. We introduce the notion of "correspondence," which is an equivalence relation between RNA elements in sets of sequences as the basis of an RNA alignment ontology. The purpose of this ontology is twofold: first, to enable the development of new representations of RNA data and of software tools that resolve the expansion problems with current RNA sequence alignments, and second, to facilitate the integration of sequence data with secondary and three-dimensional structural information, as well as other experimental information, to create simultaneously more accurate and more exploitable RNA alignments.
2008
Acker J., Ozanne C., Kachouri-Lafond R., Gaillardin C., Neuveglise C., Marck C.
Dicistronic tRNA-5S rRNA genes in Yarrowia lipolytica: an alternative TFIIIA-independent way for expression of 5S rRNA genes Journal Article
In: Nucleic Acids Res, vol. 36, no. 18, pp. 5832-44, 2008, (1362-4962 (Electronic) Journal Article Research Support, Non-U.S. Gov't).
Abstract | BibTeX | Tags: WESTHOF
@article{,
title = {Dicistronic tRNA-5S rRNA genes in Yarrowia lipolytica: an alternative TFIIIA-independent way for expression of 5S rRNA genes},
author = { J. Acker and C. Ozanne and R. Kachouri-Lafond and C. Gaillardin and C. Neuveglise and C. Marck},
year = {2008},
date = {2008-01-01},
journal = {Nucleic Acids Res},
volume = {36},
number = {18},
pages = {5832-44},
abstract = {In eukaryotes, genes transcribed by RNA polymerase III (Pol III) carry their own internal promoters and as such, are transcribed as individual units. Indeed, a very few cases of dicistronic Pol III genes are yet known. In contrast to other hemiascomycetes, 5S rRNA genes of Yarrowia lipolytica are not embedded into the tandemly repeated rDNA units, but appear scattered throughout the genome. We report here an unprecedented genomic organization: 48 over the 108 copies of the 5S rRNA genes are located 3' of tRNA genes. We show that these peculiar tRNA-5S rRNA dicistronic genes are expressed in vitro and in vivo as Pol III transcriptional fusions without the need of the 5S rRNA gene-specific factor TFIIIA, the deletion of which displays a viable phenotype. We also report the existence of a novel putative non-coding Pol III RNA of unknown function about 70 nucleotide-long (RUF70), the 13 genes of which are devoid of internal Pol III promoters and located 3' of the 13 copies of the tDNA-Trp (CCA). All genes embedded in the various dicistronic genes, fused 5S rRNA genes, RUF70 genes and their leader tRNA genes appear to be efficiently transcribed and their products correctly processed in vivo.},
note = {1362-4962 (Electronic)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {WESTHOF},
pubstate = {published},
tppubtype = {article}
}
In eukaryotes, genes transcribed by RNA polymerase III (Pol III) carry their own internal promoters and as such, are transcribed as individual units. Indeed, a very few cases of dicistronic Pol III genes are yet known. In contrast to other hemiascomycetes, 5S rRNA genes of Yarrowia lipolytica are not embedded into the tandemly repeated rDNA units, but appear scattered throughout the genome. We report here an unprecedented genomic organization: 48 over the 108 copies of the 5S rRNA genes are located 3' of tRNA genes. We show that these peculiar tRNA-5S rRNA dicistronic genes are expressed in vitro and in vivo as Pol III transcriptional fusions without the need of the 5S rRNA gene-specific factor TFIIIA, the deletion of which displays a viable phenotype. We also report the existence of a novel putative non-coding Pol III RNA of unknown function about 70 nucleotide-long (RUF70), the 13 genes of which are devoid of internal Pol III promoters and located 3' of the 13 copies of the tDNA-Trp (CCA). All genes embedded in the various dicistronic genes, fused 5S rRNA genes, RUF70 genes and their leader tRNA genes appear to be efficiently transcribed and their products correctly processed in vivo.
Nielsen H, Beckert B, Masquida B, Johansen S D
The GIR1 branching ribozymes Book Chapter
In: Lilley, D M J; Eckstein, F (Ed.): Ribozymes and RNA catalysis, pp. 229-252, Royal Society of Chemistry, Cambridge, 2008, ISBN: 0.1039/9781847557988-00229.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@inbook{,
title = {The GIR1 branching ribozymes},
author = {H Nielsen and B Beckert and B Masquida and S D Johansen},
editor = {D M J Lilley and F Eckstein},
url = {http://pubs.rsc.org/en/content/chapter/bk9780854042531-00229/978-0-85404-253-1},
isbn = {0.1039/9781847557988-00229},
year = {2008},
date = {2008-01-01},
booktitle = {Ribozymes and RNA catalysis},
pages = {229-252},
publisher = {Royal Society of Chemistry},
address = {Cambridge},
abstract = {The GIR1 branching ribozyme is a ca. 179 nt ribozyme with structural resemblance to group I ribozymes.1 It is found within a complex type of group I introns, termed the twin-ribozyme introns.2 Rather than splicing, it catalyses a branching reaction in which the 2′OH of an internal residue is involve.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {inbook}
}
The GIR1 branching ribozyme is a ca. 179 nt ribozyme with structural resemblance to group I ribozymes.1 It is found within a complex type of group I introns, termed the twin-ribozyme introns.2 Rather than splicing, it catalyses a branching reaction in which the 2′OH of an internal residue is involve.
Kisseleva N, Khvorova A, Westhof E, Schiemann O, Wolfson A D
In: Oligonucleotides, vol. 18, no. 2, pp. 101-110, 2008, ISBN: 10.1089/oli.2008.0129..
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {The different role of high-affinity and low-affinity metal ions in cleavage by a tertiary stabilized cis hammerhead ribozyme from tobacco ringspot virus},
author = {N Kisseleva and A Khvorova and E Westhof and O Schiemann and A D Wolfson},
url = {http://online.liebertpub.com/doi/abs/10.1089/oli.2008.0129},
isbn = {10.1089/oli.2008.0129.},
year = {2008},
date = {2008-01-01},
journal = {Oligonucleotides},
volume = {18},
number = {2},
pages = {101-110},
abstract = {The aim of this study was to investigate the dependence of the observed cleavage rates (kobs) of a tertiary stabilized hammerhead ribozyme (tsHHRz) and of a minimal hammerhead ribozyme (mHHRz), both derived from tobacco ringspot virus, on the type and concentration of divalent metal ions in order to interpret the functional role of high-affinity ions detected by electron paramagnetic resonance (EPR). To measure the fast cleavage of the cis tsHHRz, a new method using chemically synthesized fluorescent-labeled RNAs has been developed. The tsHHRz cleavage rate is up to 20-fold faster than that of the mHHRz under similar conditions. The presence of Mn2+ ions leads to a 60-fold faster cleavage than in the presence of Mg2+ ions. The functional role of the high-affinity ion was evaluated using neomycin B inhibition studies. Neomycin B reduces the cleavage activity of both ribozymes but the inhibitory effect on tsHHRz is much weaker than that on the mHHRz. EPR data had shown that neomycin B displaces both low-affinity and high-affinity Mn2+ ions from the mHHRz, but only low-affinity ions from tsHHRz. Inhibition of the tsHHRz activity may be due to the displacement of weakly bound Me2+ ions required for the local folding leading to cleavage, whereas both the high-affinity ion required for folding and the weakly bound ions are replaced in the mHHRz. The high-affinity metal ion is required for the stabilization of the global HHRz structure, but is not involved in catalysis or stabilization of the transient state.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The aim of this study was to investigate the dependence of the observed cleavage rates (kobs) of a tertiary stabilized hammerhead ribozyme (tsHHRz) and of a minimal hammerhead ribozyme (mHHRz), both derived from tobacco ringspot virus, on the type and concentration of divalent metal ions in order to interpret the functional role of high-affinity ions detected by electron paramagnetic resonance (EPR). To measure the fast cleavage of the cis tsHHRz, a new method using chemically synthesized fluorescent-labeled RNAs has been developed. The tsHHRz cleavage rate is up to 20-fold faster than that of the mHHRz under similar conditions. The presence of Mn2+ ions leads to a 60-fold faster cleavage than in the presence of Mg2+ ions. The functional role of the high-affinity ion was evaluated using neomycin B inhibition studies. Neomycin B reduces the cleavage activity of both ribozymes but the inhibitory effect on tsHHRz is much weaker than that on the mHHRz. EPR data had shown that neomycin B displaces both low-affinity and high-affinity Mn2+ ions from the mHHRz, but only low-affinity ions from tsHHRz. Inhibition of the tsHHRz activity may be due to the displacement of weakly bound Me2+ ions required for the local folding leading to cleavage, whereas both the high-affinity ion required for folding and the weakly bound ions are replaced in the mHHRz. The high-affinity metal ion is required for the stabilization of the global HHRz structure, but is not involved in catalysis or stabilization of the transient state.
Hashem Y, Westhof E, Auffinger P
Milestones in RNA molecular dynamics simulations Book Chapter
In: Schwede, T; Peitsch, M C (Ed.): Computational structural biology, vol. 13, pp. 363-399, World Scientific Publishing Co, 2008.
Links | BibTeX | Tags: Unité ARN, WESTHOF
@inbook{,
title = {Milestones in RNA molecular dynamics simulations},
author = {Y Hashem and E Westhof and P Auffinger},
editor = {T Schwede and M C Peitsch},
url = {http://ebooks.worldscinet.com/ISBN/9789812778789/9789812778789_0013.html},
year = {2008},
date = {2008-01-01},
booktitle = {Computational structural biology},
volume = {13},
pages = {363-399},
publisher = {World Scientific Publishing Co},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {inbook}
}
Acker J, Ozanne C, Kachouri-Lafond R, Gaillardin C, Neuveglise C, Marck C
Dicistronic tRNA-5S rRNA genes in Yarrowia lipolytica: an alternative TFIIIA-independent way for expression of 5S rRNA genes Journal Article
In: Nucleic Acids Res, vol. 36, no. 18, pp. 5832-5844, 2008, ISBN: 18790808, (1362-4962 (Electronic) Journal Article Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Dicistronic tRNA-5S rRNA genes in Yarrowia lipolytica: an alternative TFIIIA-independent way for expression of 5S rRNA genes},
author = {J Acker and C Ozanne and R Kachouri-Lafond and C Gaillardin and C Neuveglise and C Marck},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18790808},
isbn = {18790808},
year = {2008},
date = {2008-01-01},
journal = {Nucleic Acids Res},
volume = {36},
number = {18},
pages = {5832-5844},
abstract = {In eukaryotes, genes transcribed by RNA polymerase III (Pol III) carry their own internal promoters and as such, are transcribed as individual units. Indeed, a very few cases of dicistronic Pol III genes are yet known. In contrast to other hemiascomycetes, 5S rRNA genes of Yarrowia lipolytica are not embedded into the tandemly repeated rDNA units, but appear scattered throughout the genome. We report here an unprecedented genomic organization: 48 over the 108 copies of the 5S rRNA genes are located 3' of tRNA genes. We show that these peculiar tRNA-5S rRNA dicistronic genes are expressed in vitro and in vivo as Pol III transcriptional fusions without the need of the 5S rRNA gene-specific factor TFIIIA, the deletion of which displays a viable phenotype. We also report the existence of a novel putative non-coding Pol III RNA of unknown function about 70 nucleotide-long (RUF70), the 13 genes of which are devoid of internal Pol III promoters and located 3' of the 13 copies of the tDNA-Trp (CCA). All genes embedded in the various dicistronic genes, fused 5S rRNA genes, RUF70 genes and their leader tRNA genes appear to be efficiently transcribed and their products correctly processed in vivo.},
note = {1362-4962 (Electronic)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
In eukaryotes, genes transcribed by RNA polymerase III (Pol III) carry their own internal promoters and as such, are transcribed as individual units. Indeed, a very few cases of dicistronic Pol III genes are yet known. In contrast to other hemiascomycetes, 5S rRNA genes of Yarrowia lipolytica are not embedded into the tandemly repeated rDNA units, but appear scattered throughout the genome. We report here an unprecedented genomic organization: 48 over the 108 copies of the 5S rRNA genes are located 3' of tRNA genes. We show that these peculiar tRNA-5S rRNA dicistronic genes are expressed in vitro and in vivo as Pol III transcriptional fusions without the need of the 5S rRNA gene-specific factor TFIIIA, the deletion of which displays a viable phenotype. We also report the existence of a novel putative non-coding Pol III RNA of unknown function about 70 nucleotide-long (RUF70), the 13 genes of which are devoid of internal Pol III promoters and located 3' of the 13 copies of the tDNA-Trp (CCA). All genes embedded in the various dicistronic genes, fused 5S rRNA genes, RUF70 genes and their leader tRNA genes appear to be efficiently transcribed and their products correctly processed in vivo.
Beniaminov A, Westhof E, Krol A
Distinctive structures between chimpanzee and human in a brain noncoding RNA Journal Article
In: RNA, vol. 14, no. 7, pp. 1270-1275, 2008, ISBN: 18511501, (1469-9001 (Electronic) Letter Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: Animals Base Sequence Brain/*metabolism Evolution, Human Humans Molecular Sequence Data Nucleic Acid Conformation Pan troglodytes/*genetics RNA, Molecular Genome, Unité ARN, Untranslated/*chemistry, WESTHOF
@article{,
title = {Distinctive structures between chimpanzee and human in a brain noncoding RNA},
author = {A Beniaminov and E Westhof and A Krol},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18511501},
isbn = {18511501},
year = {2008},
date = {2008-01-01},
journal = {RNA},
volume = {14},
number = {7},
pages = {1270-1275},
abstract = {Human accelerated region 1 (HAR1) is a short DNA region identified recently to have evolved the most rapidly among highly constrained regions since the divergence from our common ancestor with chimpanzee. It is transcribed as part of a noncoding RNA specifically expressed in the developing human neocortex. Employing a panoply of enzymatic and chemical probes, our analysis of HAR1 RNA proposed a secondary structure model differing from that published. Most surprisingly, we discovered that the substitutions between the chimpanzee and human sequences led the human HAR1 RNA to adopt a cloverleaf-like structure instead of an extended and unstable hairpin in the chimpanzee sequence. Thus, the rapid evolutionary changes resulted in a profound rearrangement of HAR1 RNA structure. Altogether, our results provide a structural context for elucidating HAR1 RNA function.},
note = {1469-9001 (Electronic)
Letter
Research Support, Non-U.S. Gov't},
keywords = {Animals Base Sequence Brain/*metabolism Evolution, Human Humans Molecular Sequence Data Nucleic Acid Conformation Pan troglodytes/*genetics RNA, Molecular Genome, Unité ARN, Untranslated/*chemistry, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Human accelerated region 1 (HAR1) is a short DNA region identified recently to have evolved the most rapidly among highly constrained regions since the divergence from our common ancestor with chimpanzee. It is transcribed as part of a noncoding RNA specifically expressed in the developing human neocortex. Employing a panoply of enzymatic and chemical probes, our analysis of HAR1 RNA proposed a secondary structure model differing from that published. Most surprisingly, we discovered that the substitutions between the chimpanzee and human sequences led the human HAR1 RNA to adopt a cloverleaf-like structure instead of an extended and unstable hairpin in the chimpanzee sequence. Thus, the rapid evolutionary changes resulted in a profound rearrangement of HAR1 RNA structure. Altogether, our results provide a structural context for elucidating HAR1 RNA function.
Kondo J, Westhof E
The bacterial and mitochondrial ribosomal A-site molecular switches possess different conformational substates Journal Article
In: Nucleic Acids Res, vol. 36, no. 8, pp. 2654-2666, 2008, ISBN: 18346970, (1362-4962 (Electronic) Journal Article).
Abstract | Links | BibTeX | Tags: Bacterial/*chemistry RNA, Crystallography, Messenger/chemistry RNA, Molecular Nucleic Acid Conformation Point Mutation RNA/*chemistry/genetics RNA, Ribosomal/*chemistry RNA, Transfer/chemistry, Unité ARN, WESTHOF, WESTHOF Crystallography, X-Ray Hearing Loss/genetics Humans Models
@article{,
title = {The bacterial and mitochondrial ribosomal A-site molecular switches possess different conformational substates},
author = {J Kondo and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18346970},
isbn = {18346970},
year = {2008},
date = {2008-01-01},
journal = {Nucleic Acids Res},
volume = {36},
number = {8},
pages = {2654-2666},
abstract = {The A site of the small ribosomal subunit participates in the fidelity of decoding by switching between two states, a resting 'off' state and an active decoding 'on' state. Eight crystal structures of RNA duplexes containing two minimal decoding A sites of the Homo sapiens mitochondrial wild-type, the A1555G mutant or bacteria have been solved. The resting 'off' state of the mitochondrial wild-type A site is surprisingly different from that of the bacterial A site. The mitochondrial A1555G mutant has two types of the 'off' states; one is similar to the mitochondrial wild-type 'off' state and the other is similar to the bacterial 'off' state. Our present results indicate that the dynamics of the A site in bacteria and mitochondria are different, a property probably related to the small number of tRNAs used for decoding in mitochondria. Based on these structures, we propose a hypothesis for the molecular mechanism of non-syndromic hearing loss due to the mitochondrial A1555G mutation.},
note = {1362-4962 (Electronic)
Journal Article},
keywords = {Bacterial/*chemistry RNA, Crystallography, Messenger/chemistry RNA, Molecular Nucleic Acid Conformation Point Mutation RNA/*chemistry/genetics RNA, Ribosomal/*chemistry RNA, Transfer/chemistry, Unité ARN, WESTHOF, WESTHOF Crystallography, X-Ray Hearing Loss/genetics Humans Models},
pubstate = {published},
tppubtype = {article}
}
The A site of the small ribosomal subunit participates in the fidelity of decoding by switching between two states, a resting 'off' state and an active decoding 'on' state. Eight crystal structures of RNA duplexes containing two minimal decoding A sites of the Homo sapiens mitochondrial wild-type, the A1555G mutant or bacteria have been solved. The resting 'off' state of the mitochondrial wild-type A site is surprisingly different from that of the bacterial A site. The mitochondrial A1555G mutant has two types of the 'off' states; one is similar to the mitochondrial wild-type 'off' state and the other is similar to the bacterial 'off' state. Our present results indicate that the dynamics of the A site in bacteria and mitochondria are different, a property probably related to the small number of tRNAs used for decoding in mitochondria. Based on these structures, we propose a hypothesis for the molecular mechanism of non-syndromic hearing loss due to the mitochondrial A1555G mutation.
Vicens Q, Paukstelis P J, Westhof E, Lambowitz A M, Cech T R
Toward predicting self-splicing and protein-facilitated splicing of group I introns Journal Article
In: RNA, vol. 14, no. 10, pp. 2013-2029, 2008, ISBN: 18768647, (1469-9001 (Electronic) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: Base Composition Base Sequence Catalysis *Introns Neurospora crassa/enzymology *Nucleic Acid Conformation *RNA Splicing RNA, Catalytic/*chemistry RNA, Messenger/*chemistry Tyrosine-tRNA Ligase/*chemistry, Unité ARN, WESTHOF, WESTHOF Base Composition Base Sequence Catalysis *Introns Neurospora crassa/enzymology *Nucleic Acid Conformation *RNA Splicing RNA
@article{,
title = {Toward predicting self-splicing and protein-facilitated splicing of group I introns},
author = {Q Vicens and P J Paukstelis and E Westhof and A M Lambowitz and T R Cech},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18768647},
isbn = {18768647},
year = {2008},
date = {2008-01-01},
journal = {RNA},
volume = {14},
number = {10},
pages = {2013-2029},
abstract = {In the current era of massive discoveries of noncoding RNAs within genomes, being able to infer a function from a nucleotide sequence is of paramount interest. Although studies of individual group I introns have identified self-splicing and nonself-splicing examples, there is no overall understanding of the prevalence of self-splicing or the factors that determine it among the >2300 group I introns sequenced to date. Here, the self-splicing activities of 12 group I introns from various organisms were assayed under six reaction conditions that had been shown previously to promote RNA catalysis for different RNAs. Besides revealing that assessing self-splicing under only one condition can be misleading, this survey emphasizes that in vitro self-splicing efficiency is correlated with the GC content of the intron (>35% GC was generally conductive to self-splicing), and with the ability of the introns to form particular tertiary interactions. Addition of the Neurospora crassa CYT-18 protein activated splicing of two nonself-splicing introns, but inhibited the second step of self-splicing for two others. Together, correlations between sequence, predicted structure and splicing begin to establish rules that should facilitate our ability to predict the self-splicing activity of any group I intron from its sequence.},
note = {1469-9001 (Electronic)
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't},
keywords = {Base Composition Base Sequence Catalysis *Introns Neurospora crassa/enzymology *Nucleic Acid Conformation *RNA Splicing RNA, Catalytic/*chemistry RNA, Messenger/*chemistry Tyrosine-tRNA Ligase/*chemistry, Unité ARN, WESTHOF, WESTHOF Base Composition Base Sequence Catalysis *Introns Neurospora crassa/enzymology *Nucleic Acid Conformation *RNA Splicing RNA},
pubstate = {published},
tppubtype = {article}
}
In the current era of massive discoveries of noncoding RNAs within genomes, being able to infer a function from a nucleotide sequence is of paramount interest. Although studies of individual group I introns have identified self-splicing and nonself-splicing examples, there is no overall understanding of the prevalence of self-splicing or the factors that determine it among the >2300 group I introns sequenced to date. Here, the self-splicing activities of 12 group I introns from various organisms were assayed under six reaction conditions that had been shown previously to promote RNA catalysis for different RNAs. Besides revealing that assessing self-splicing under only one condition can be misleading, this survey emphasizes that in vitro self-splicing efficiency is correlated with the GC content of the intron (>35% GC was generally conductive to self-splicing), and with the ability of the introns to form particular tertiary interactions. Addition of the Neurospora crassa CYT-18 protein activated splicing of two nonself-splicing introns, but inhibited the second step of self-splicing for two others. Together, correlations between sequence, predicted structure and splicing begin to establish rules that should facilitate our ability to predict the self-splicing activity of any group I intron from its sequence.
2007
Santini G P, Pakleza C, Auffinger P, Moriou C, Favre A, Clivio P, Cognet J A
Dinucleotide TpT and Its 2'-O-Me Analogue Possess Different Backbone Conformations and Flexibilities but Similar Stacked Geometries Journal Article
In: J Phys Chem B, vol. 111, no. 31, pp. 9400-9409, 2007, ISBN: 17625827, (1520-6106 (Print) Journal article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Dinucleotide TpT and Its 2'-O-Me Analogue Possess Different Backbone Conformations and Flexibilities but Similar Stacked Geometries},
author = {G P Santini and C Pakleza and P Auffinger and C Moriou and A Favre and P Clivio and J A Cognet},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17625827},
isbn = {17625827},
year = {2007},
date = {2007-01-01},
journal = {J Phys Chem B},
volume = {111},
number = {31},
pages = {9400-9409},
abstract = {UV irradiation at 254 nm of 2'-O,5-dimethyluridylyl(3'-5')-2'-O,5-dimethyluridine (1a) and of natural thymidylyl(3'-5')thymidine (1b) generates the same photoproducts (CPD and (6-4)PP; responsible for cell death and skin cancer). The ratios of quantum yields of photoproducts obtained from 1a (determined herein) to that from 1b are in a proportion close to the approximately threefold increase of stacked dinucleotides for 1a compared with those of 1b (from previous circular dichroism results). 1a and 1b however are endowed with different predominant sugar conformations, C3'-endo (1a) and C2'-endo (1b). The present investigation of the stacked conformation of these molecules, by unrestrained state-of-the-art molecular simulation in explicit solvent and salt, resolves this apparent paradox and suggests the following main conclusions. Stacked dinucleotides 1a and 1b adopt the main characteristic features of a single-stranded A and B form, respectively, where the relative positions of the backbone and the bases are very different. Unexpectedly, the geometry of the stacking of two thymine bases, within each dinucleotide, is very similar and is in excellent agreement with photochemical and circular dichroism results. Analyses of molecular dynamics trajectories with conformational adiabatic mapping show that 1a and 1b explore two different regions of conformational space and possess very different flexibilities. Therefore, even though their base stacking is very similar, these molecules possess different geometrical, mechanical, and dynamical properties that may account for the discrepancy observed between increased stacking and increased photoproduct formations. The computed average stacked conformations of 1a and 1b are well-defined and could serve as starting models to investigate photochemical reactions with quantum dynamics simulations.},
note = {1520-6106 (Print)
Journal article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
UV irradiation at 254 nm of 2'-O,5-dimethyluridylyl(3'-5')-2'-O,5-dimethyluridine (1a) and of natural thymidylyl(3'-5')thymidine (1b) generates the same photoproducts (CPD and (6-4)PP; responsible for cell death and skin cancer). The ratios of quantum yields of photoproducts obtained from 1a (determined herein) to that from 1b are in a proportion close to the approximately threefold increase of stacked dinucleotides for 1a compared with those of 1b (from previous circular dichroism results). 1a and 1b however are endowed with different predominant sugar conformations, C3'-endo (1a) and C2'-endo (1b). The present investigation of the stacked conformation of these molecules, by unrestrained state-of-the-art molecular simulation in explicit solvent and salt, resolves this apparent paradox and suggests the following main conclusions. Stacked dinucleotides 1a and 1b adopt the main characteristic features of a single-stranded A and B form, respectively, where the relative positions of the backbone and the bases are very different. Unexpectedly, the geometry of the stacking of two thymine bases, within each dinucleotide, is very similar and is in excellent agreement with photochemical and circular dichroism results. Analyses of molecular dynamics trajectories with conformational adiabatic mapping show that 1a and 1b explore two different regions of conformational space and possess very different flexibilities. Therefore, even though their base stacking is very similar, these molecules possess different geometrical, mechanical, and dynamical properties that may account for the discrepancy observed between increased stacking and increased photoproduct formations. The computed average stacked conformations of 1a and 1b are well-defined and could serve as starting models to investigate photochemical reactions with quantum dynamics simulations.
Westhof E
A tale in molecular recognition: the hammerhead ribozyme Journal Article
In: J Mol Recognit, vol. 20, no. 1, pp. 1-3, 2007, ISBN: 17089350, (0952-3499 (Print) Journal Article).
Abstract | Links | BibTeX | Tags: Animals Base Sequence Catalysis Molecular Sequence Data Nucleic Acid Conformation RNA, Catalytic/chemistry/genetics/*metabolism Schistosoma mansoni/chemistry, Unité ARN, WESTHOF, WESTHOF Animals Base Sequence Catalysis Molecular Sequence Data Nucleic Acid Conformation RNA
@article{,
title = {A tale in molecular recognition: the hammerhead ribozyme},
author = {E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17089350},
isbn = {17089350},
year = {2007},
date = {2007-01-01},
journal = {J Mol Recognit},
volume = {20},
number = {1},
pages = {1-3},
abstract = {A new crystal structure of the hammerhead ribozyme demonstrates the influence of peripheral tertiary contacts on the local conformations around the active site. This structure resolves many conflicting results obtained on reduced systems.},
note = {0952-3499 (Print)
Journal Article},
keywords = {Animals Base Sequence Catalysis Molecular Sequence Data Nucleic Acid Conformation RNA, Catalytic/chemistry/genetics/*metabolism Schistosoma mansoni/chemistry, Unité ARN, WESTHOF, WESTHOF Animals Base Sequence Catalysis Molecular Sequence Data Nucleic Acid Conformation RNA},
pubstate = {published},
tppubtype = {article}
}
A new crystal structure of the hammerhead ribozyme demonstrates the influence of peripheral tertiary contacts on the local conformations around the active site. This structure resolves many conflicting results obtained on reduced systems.
2006
Vaiana A C, Westhof E, Auffinger P
A molecular dynamics simulation study of an aminoglycoside/A-site RNA complex: conformational and hydration patterns Journal Article
In: Biochimie, vol. 88, no. 8, pp. 1061-1073, 2006, ISBN: 16824662, (0300-9084 (Print) Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {A molecular dynamics simulation study of an aminoglycoside/A-site RNA complex: conformational and hydration patterns},
author = {A C Vaiana and E Westhof and P Auffinger},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16824662},
isbn = {16824662},
year = {2006},
date = {2006-01-01},
journal = {Biochimie},
volume = {88},
number = {8},
pages = {1061-1073},
abstract = {Aminoglycoside antibiotics interfere with the translation mechanism by binding to the tRNA decoding site of the 16S ribosomal RNA. Crystallographic structures of aminoglycosides bound to A-site systems clarified many static aspects of RNA-ligand interactions. To gain some insight on the dynamic aspects of recognition phenomena, we conducted molecular dynamics simulations of the aminoglycoside paromomycin bound to a eubacterial ribosomal decoding A-site oligonucleotide. Results from 25 ns of simulation time revealed that: (i) the neamine part of the antibiotic represents the main anchor for binding, (ii) additional sugar rings provide limited and fragile contacts, (iii) long-resident water molecules present at the drug/RNA interface are involved in the recognition phenomena. The combination of MD simulations together with systematic structural information offers striking insights into the molecular recognition processes underlying RNA/aminoglycoside binding. Important methodological considerations related to the use of medium resolution starting structures and associated sampling problems are thoroughly discussed.},
note = {0300-9084 (Print)
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Aminoglycoside antibiotics interfere with the translation mechanism by binding to the tRNA decoding site of the 16S ribosomal RNA. Crystallographic structures of aminoglycosides bound to A-site systems clarified many static aspects of RNA-ligand interactions. To gain some insight on the dynamic aspects of recognition phenomena, we conducted molecular dynamics simulations of the aminoglycoside paromomycin bound to a eubacterial ribosomal decoding A-site oligonucleotide. Results from 25 ns of simulation time revealed that: (i) the neamine part of the antibiotic represents the main anchor for binding, (ii) additional sugar rings provide limited and fragile contacts, (iii) long-resident water molecules present at the drug/RNA interface are involved in the recognition phenomena. The combination of MD simulations together with systematic structural information offers striking insights into the molecular recognition processes underlying RNA/aminoglycoside binding. Important methodological considerations related to the use of medium resolution starting structures and associated sampling problems are thoroughly discussed.
Rhode B M, Hartmuth K, Westhof E, Luhrmann R
Proximity of conserved U6 and U2 snRNA elements to the 5' splice site region in activated spliceosomes Journal Article
In: EMBO J, vol. 25, no. 11, pp. 2475-2486, 2006, ISBN: 16688215, (0261-4189 (Print) Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Proximity of conserved U6 and U2 snRNA elements to the 5' splice site region in activated spliceosomes},
author = {B M Rhode and K Hartmuth and E Westhof and R Luhrmann},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16688215},
isbn = {16688215},
year = {2006},
date = {2006-01-01},
journal = {EMBO J},
volume = {25},
number = {11},
pages = {2475-2486},
abstract = {Major structural changes occur in the spliceosome during its catalytic activation, which immediately precedes the splicing of pre-mRNA. Whereas changes in snRNA conformation are well documented at the level of secondary RNA-RNA interactions, little is known about the tertiary structure of this RNA-RNA network, which comprises the spliceosome's catalytic core. Here, we have used the hydroxyl-radical probe Fe-BABE, tethered to the tenth nucleotide (U(+10)) of the 5' end of a pre-mRNA intron, to map RNA-RNA proximities in spliceosomes. These studies revealed that several conserved snRNA regions are close to U(+10) in activated spliceosomes, namely (i) the U6 snRNA ACAGAG-box region, (ii) portions of the U6 intramolecular stem-loop (U6-ISL) including a nucleotide implicated in the first catalytic step (U74), and (iii) the region of U2 that interacts with the branch point. These data constrain the relative orientation of these structural elements with respect to U(+10) in the activated spliceosome. Upon conversion of the activated spliceosome to complex C, the accessibility of U6-ISL to hydroxyl-radical cleavage is altered, suggesting rearrangements after the first catalytic step.},
note = {0261-4189 (Print)
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Major structural changes occur in the spliceosome during its catalytic activation, which immediately precedes the splicing of pre-mRNA. Whereas changes in snRNA conformation are well documented at the level of secondary RNA-RNA interactions, little is known about the tertiary structure of this RNA-RNA network, which comprises the spliceosome's catalytic core. Here, we have used the hydroxyl-radical probe Fe-BABE, tethered to the tenth nucleotide (U(+10)) of the 5' end of a pre-mRNA intron, to map RNA-RNA proximities in spliceosomes. These studies revealed that several conserved snRNA regions are close to U(+10) in activated spliceosomes, namely (i) the U6 snRNA ACAGAG-box region, (ii) portions of the U6 intramolecular stem-loop (U6-ISL) including a nucleotide implicated in the first catalytic step (U74), and (iii) the region of U2 that interacts with the branch point. These data constrain the relative orientation of these structural elements with respect to U(+10) in the activated spliceosome. Upon conversion of the activated spliceosome to complex C, the accessibility of U6-ISL to hydroxyl-radical cleavage is altered, suggesting rearrangements after the first catalytic step.
Masquida B, Westhof E
A Modular and Hierarchical Approach for All-Atom RNA Modeling Book Chapter
In: F., Cech Atkins T J Gesteland R. (Ed.): The RNA World, Third Edition, pp. 659-681, Cold Spring Harbor Laboratory Press, 2006.
Links | BibTeX | Tags: Unité ARN, WESTHOF
@inbook{,
title = {A Modular and Hierarchical Approach for All-Atom RNA Modeling},
author = {B Masquida and E Westhof},
editor = {Cech Atkins T J Gesteland R. F.},
url = {http://cshmonographs.org/index.php/monographs/article/viewArticle/3749},
doi = {10.1101/087969739.43.659},
year = {2006},
date = {2006-01-01},
booktitle = {The RNA World, Third Edition},
pages = {659-681},
publisher = {Cold Spring Harbor Laboratory Press},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {inbook}
}
Marck C, Kachouri-Lafond R, Lafontaine I, Westhof E, Dujon B, Grosjean H
In: Nucleic Acids Res, vol. 34, no. 6, pp. 1816-1835, 2006, ISBN: 16600899, (1362-4962 (Electronic) Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {The RNA polymerase III-dependent family of genes in hemiascomycetes: comparative RNomics, decoding strategies, transcription and evolutionary implications},
author = {C Marck and R Kachouri-Lafond and I Lafontaine and E Westhof and B Dujon and H Grosjean},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16600899},
isbn = {16600899},
year = {2006},
date = {2006-01-01},
journal = {Nucleic Acids Res},
volume = {34},
number = {6},
pages = {1816-1835},
abstract = {We present the first comprehensive analysis of RNA polymerase III (Pol III) transcribed genes in ten yeast genomes. This set includes all tRNA genes (tDNA) and genes coding for SNR6 (U6), SNR52, SCR1 and RPR1 RNA in the nine hemiascomycetes Saccharomyces cerevisiae, Saccharomyces castellii, Candida glabrata, Kluyveromyces waltii, Kluyveromyces lactis, Eremothecium gossypii, Debaryomyces hansenii, Candida albicans, Yarrowia lipolytica and the archiascomycete Schizosaccharomyces pombe. We systematically analysed sequence specificities of tRNA genes, polymorphism, variability of introns, gene redundancy and gene clustering. Analysis of decoding strategies showed that yeasts close to S.cerevisiae use bacterial decoding rules to read the Leu CUN and Arg CGN codons, in contrast to all other known Eukaryotes. In D.hansenii and C.albicans, we identified a novel tDNA-Leu (AAG), reading the Leu CUU/CUC/CUA codons with an unusual G at position 32. A systematic 'p-distance tree' using the 60 variable positions of the tRNA molecule revealed that most tDNAs cluster into amino acid-specific sub-trees, suggesting that, within hemiascomycetes, orthologous tDNAs are more closely related than paralogs. We finally determined the bipartite A- and B-box sequences recognized by TFIIIC. These minimal sequences are nearly conserved throughout hemiascomycetes and were satisfactorily retrieved at appropriate locations in other Pol III genes.},
note = {1362-4962 (Electronic)
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
We present the first comprehensive analysis of RNA polymerase III (Pol III) transcribed genes in ten yeast genomes. This set includes all tRNA genes (tDNA) and genes coding for SNR6 (U6), SNR52, SCR1 and RPR1 RNA in the nine hemiascomycetes Saccharomyces cerevisiae, Saccharomyces castellii, Candida glabrata, Kluyveromyces waltii, Kluyveromyces lactis, Eremothecium gossypii, Debaryomyces hansenii, Candida albicans, Yarrowia lipolytica and the archiascomycete Schizosaccharomyces pombe. We systematically analysed sequence specificities of tRNA genes, polymorphism, variability of introns, gene redundancy and gene clustering. Analysis of decoding strategies showed that yeasts close to S.cerevisiae use bacterial decoding rules to read the Leu CUN and Arg CGN codons, in contrast to all other known Eukaryotes. In D.hansenii and C.albicans, we identified a novel tDNA-Leu (AAG), reading the Leu CUU/CUC/CUA codons with an unusual G at position 32. A systematic 'p-distance tree' using the 60 variable positions of the tRNA molecule revealed that most tDNAs cluster into amino acid-specific sub-trees, suggesting that, within hemiascomycetes, orthologous tDNAs are more closely related than paralogs. We finally determined the bipartite A- and B-box sequences recognized by TFIIIC. These minimal sequences are nearly conserved throughout hemiascomycetes and were satisfactorily retrieved at appropriate locations in other Pol III genes.
Lescoute A, Westhof E
The A-minor motifs in the decoding recognition process Journal Article
In: Biochimie, vol. 88, no. 8, pp. 993-999, 2006, ISBN: 16889885, (0300-9084 (Print) Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {The A-minor motifs in the decoding recognition process},
author = {A Lescoute and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16889885},
isbn = {16889885},
year = {2006},
date = {2006-01-01},
journal = {Biochimie},
volume = {88},
number = {8},
pages = {993-999},
abstract = {The formation of A-minor motifs, mediated by adenines binding into the shallow/minor groove of stacked and helical Watson-Crick base pairs, is described. The conformations of the bacterial ribosomal decoding A site in various crystal structures are reviewed. The adenines A1492 and A1493 of the A site are seen either tucked in within the internal loop or bulging out and poised for interaction. This dynamic equilibrium contributes to the decoding process of the codon:anticodon base pairings. Aminoglycoside antibiotics lock the conformation of the A site in a single state with bulged-out adenines and thereby disrupt regulation of the decoding process.},
note = {0300-9084 (Print)
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The formation of A-minor motifs, mediated by adenines binding into the shallow/minor groove of stacked and helical Watson-Crick base pairs, is described. The conformations of the bacterial ribosomal decoding A site in various crystal structures are reviewed. The adenines A1492 and A1493 of the A site are seen either tucked in within the internal loop or bulging out and poised for interaction. This dynamic equilibrium contributes to the decoding process of the codon:anticodon base pairings. Aminoglycoside antibiotics lock the conformation of the A site in a single state with bulged-out adenines and thereby disrupt regulation of the decoding process.
Leontis N B, Altman R B, Berman H M, Brenner S E, Brown J W, Engelke D R, Harvey S C, Holbrook S R, Jossinet F, Lewis S E, Major F, Mathews D H, Richardson J S, Williamson J R, Westhof E
The RNA Ontology Consortium: an open invitation to the RNA community Journal Article
In: RNA, vol. 12, no. 4, pp. 533-541, 2006, ISBN: 16484377, (1355-8382 (Print) Letter).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {The RNA Ontology Consortium: an open invitation to the RNA community},
author = {N B Leontis and R B Altman and H M Berman and S E Brenner and J W Brown and D R Engelke and S C Harvey and S R Holbrook and F Jossinet and S E Lewis and F Major and D H Mathews and J S Richardson and J R Williamson and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16484377},
isbn = {16484377},
year = {2006},
date = {2006-01-01},
journal = {RNA},
volume = {12},
number = {4},
pages = {533-541},
abstract = {The aim of the RNA Ontology Consortium (ROC) is to create an integrated conceptual framework-an RNA Ontology (RO)-with a common, dynamic, controlled, and structured vocabulary to describe and characterize RNA sequences, secondary structures, three-dimensional structures, and dynamics pertaining to RNA function. The RO should produce tools for clear communication about RNA structure and function for multiple uses, including the integration of RNA electronic resources into the Semantic Web. These tools should allow the accurate description in computer-interpretable form of the coupling between RNA architecture, function, and evolution. The purposes for creating the RO are, therefore, (1) to integrate sequence and structural databases; (2) to allow different computational tools to interoperate; (3) to create powerful software tools that bring advanced computational methods to the bench scientist; and (4) to facilitate precise searches for all relevant information pertaining to RNA. For example, one initial objective of the ROC is to define, identify, and classify RNA structural motifs described in the literature or appearing in databases and to agree on a computer-interpretable definition for each of these motifs. To achieve these aims, the ROC will foster communication and promote collaboration among RNA scientists by coordinating frequent face-to-face workshops to discuss, debate, and resolve difficult conceptual issues. These meeting opportunities will create new directions at various levels of RNA research. The ROC will work closely with the PDB/NDB structural databases and the Gene, Sequence, and Open Biomedical Ontology Consortia to integrate the RO with existing biological ontologies to extend existing content while maintaining interoperability.},
note = {1355-8382 (Print)
Letter},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The aim of the RNA Ontology Consortium (ROC) is to create an integrated conceptual framework-an RNA Ontology (RO)-with a common, dynamic, controlled, and structured vocabulary to describe and characterize RNA sequences, secondary structures, three-dimensional structures, and dynamics pertaining to RNA function. The RO should produce tools for clear communication about RNA structure and function for multiple uses, including the integration of RNA electronic resources into the Semantic Web. These tools should allow the accurate description in computer-interpretable form of the coupling between RNA architecture, function, and evolution. The purposes for creating the RO are, therefore, (1) to integrate sequence and structural databases; (2) to allow different computational tools to interoperate; (3) to create powerful software tools that bring advanced computational methods to the bench scientist; and (4) to facilitate precise searches for all relevant information pertaining to RNA. For example, one initial objective of the ROC is to define, identify, and classify RNA structural motifs described in the literature or appearing in databases and to agree on a computer-interpretable definition for each of these motifs. To achieve these aims, the ROC will foster communication and promote collaboration among RNA scientists by coordinating frequent face-to-face workshops to discuss, debate, and resolve difficult conceptual issues. These meeting opportunities will create new directions at various levels of RNA research. The ROC will work closely with the PDB/NDB structural databases and the Gene, Sequence, and Open Biomedical Ontology Consortia to integrate the RO with existing biological ontologies to extend existing content while maintaining interoperability.
Kondo J, Francois B, Urzhumtsev A, Westhof E
Crystal structure of the homo sapiens cytoplasmic ribosomal decoding site complexed with apramycin Journal Article
In: Angew Chem Int Ed Engl, vol. 45, no. 20, pp. 3310-3314, 2006, ISBN: 16596680, (0570-0833 (Print) Journal Article).
Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Crystal structure of the homo sapiens cytoplasmic ribosomal decoding site complexed with apramycin},
author = {J Kondo and B Francois and A Urzhumtsev and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16596680},
isbn = {16596680},
year = {2006},
date = {2006-01-01},
journal = {Angew Chem Int Ed Engl},
volume = {45},
number = {20},
pages = {3310-3314},
note = {0570-0833 (Print)
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Kondo J, Francois B, Russell R J, Murray J B, Westhof E
Crystal structure of the bacterial ribosomal decoding site complexed with amikacin containing the gamma-amino-alpha-hydroxybutyryl (haba) group Journal Article
In: Biochimie, vol. 88, no. 8, pp. 1027-1031, 2006, ISBN: 16806634, (0300-9084 (Print) Journal article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Crystal structure of the bacterial ribosomal decoding site complexed with amikacin containing the gamma-amino-alpha-hydroxybutyryl (haba) group},
author = {J Kondo and B Francois and R J Russell and J B Murray and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16806634},
isbn = {16806634},
year = {2006},
date = {2006-01-01},
journal = {Biochimie},
volume = {88},
number = {8},
pages = {1027-1031},
abstract = {Amikacin is the 4,6-linked aminoglycoside modified at position N1 of the 2-deoxystreptamine ring (ring II) by the L-haba group. In the present study, the crystal structure of a complex between oligonucleotide containing the bacterial ribosomal A site and amikacin has been solved at 2.7 A resolution. Amikacin specifically binds to the A site in practically the same way as its parent compound kanamycin. In addition, the L-haba group interacts with the upper side of the A site through two direct contacts, O2*.H-N4(C1496) and N4*-H.O6(G1497). The present crystal structure shows how the introduction of the L-haba group on ring II of aminoglycoside is an effective mutation for obtaining a higher affinity to the bacterial A site.},
note = {0300-9084 (Print)
Journal article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Amikacin is the 4,6-linked aminoglycoside modified at position N1 of the 2-deoxystreptamine ring (ring II) by the L-haba group. In the present study, the crystal structure of a complex between oligonucleotide containing the bacterial ribosomal A site and amikacin has been solved at 2.7 A resolution. Amikacin specifically binds to the A site in practically the same way as its parent compound kanamycin. In addition, the L-haba group interacts with the upper side of the A site through two direct contacts, O2*.H-N4(C1496) and N4*-H.O6(G1497). The present crystal structure shows how the introduction of the L-haba group on ring II of aminoglycoside is an effective mutation for obtaining a higher affinity to the bacterial A site.
Hobbie S N, Pfister P, Bruell C, Sander P, Francois B, Westhof E, Bottger E C
Binding of neomycin-class aminoglycoside antibiotics to mutant ribosomes with alterations in the A site of 16S rRNA Journal Article
In: Antimicrob Agents Chemother, vol. 50, no. 4, pp. 1489-1496, 2006, ISBN: 16569869, (0066-4804 (Print) Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Binding of neomycin-class aminoglycoside antibiotics to mutant ribosomes with alterations in the A site of 16S rRNA},
author = {S N Hobbie and P Pfister and C Bruell and P Sander and B Francois and E Westhof and E C Bottger},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16569869},
isbn = {16569869},
year = {2006},
date = {2006-01-01},
journal = {Antimicrob Agents Chemother},
volume = {50},
number = {4},
pages = {1489-1496},
abstract = {Aminoglycoside antibiotics that bind to the aminoacyl-tRNA site (A site) of the ribosome are composed of a common neamine core in which a glycopyranosyl ring is attached to position 4 of a 2-deoxystreptamine moiety. The core is further substituted by one (ribostamycin), two (neomycin and paromomycin), or three (lividomycin A) additional sugars attached to position 5 of the 2-deoxystreptamine. To study the role of rings III, IV, and V in aminoglycoside binding, we used isogenic Mycobacterium smegmatis DeltarrnB mutants carrying homogeneous populations of mutant ribosomes with alterations in the 16S rRNA A site. MICs were determined to investigate drug-ribosome interactions, and the results were compared with that of the previously published crystal structure of paromomycin bound to the ribosomal A site. Our analysis demonstrates that the stacking interaction between ring I and G1491 is largely sequence independent, that rings III and IV each increase the strength of drug binding to the ribosome, that ring IV of the 6'-NH3+ aminoglycosides compensates for loss of interactions between ring II and U1495 and between ring III and G1491, that the aminoglycosides rely on pseudo-base pairing between ring I and A1408 for binding independently of the number of sugar rings attached to the neamine core, that addition of ring V to the 6'-OH 4,5-aminoglycoside paromomycin does not alter the mode of binding, and that alteration of the U1406.U1495 wobble base pair to the Watson-Crick interaction pair 1406C-1495G yields ribosomal drug susceptibilities to 4,5-aminoglycosides comparable to those seen with the wild-type A site.},
note = {0066-4804 (Print)
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Aminoglycoside antibiotics that bind to the aminoacyl-tRNA site (A site) of the ribosome are composed of a common neamine core in which a glycopyranosyl ring is attached to position 4 of a 2-deoxystreptamine moiety. The core is further substituted by one (ribostamycin), two (neomycin and paromomycin), or three (lividomycin A) additional sugars attached to position 5 of the 2-deoxystreptamine. To study the role of rings III, IV, and V in aminoglycoside binding, we used isogenic Mycobacterium smegmatis DeltarrnB mutants carrying homogeneous populations of mutant ribosomes with alterations in the 16S rRNA A site. MICs were determined to investigate drug-ribosome interactions, and the results were compared with that of the previously published crystal structure of paromomycin bound to the ribosomal A site. Our analysis demonstrates that the stacking interaction between ring I and G1491 is largely sequence independent, that rings III and IV each increase the strength of drug binding to the ribosome, that ring IV of the 6'-NH3+ aminoglycosides compensates for loss of interactions between ring II and U1495 and between ring III and G1491, that the aminoglycosides rely on pseudo-base pairing between ring I and A1408 for binding independently of the number of sugar rings attached to the neamine core, that addition of ring V to the 6'-OH 4,5-aminoglycoside paromomycin does not alter the mode of binding, and that alteration of the U1406.U1495 wobble base pair to the Watson-Crick interaction pair 1406C-1495G yields ribosomal drug susceptibilities to 4,5-aminoglycosides comparable to those seen with the wild-type A site.
Wirmer J, Westhof E
Molecular contacts between antibiotics and the 30S ribosomal particle Journal Article
In: Methods Enzymol, vol. 415, pp. 180-202, 2006, ISBN: 17116475, (0076-6879 (Print) Journal Article Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Molecular contacts between antibiotics and the 30S ribosomal particle},
author = {J Wirmer and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17116475},
isbn = {17116475},
year = {2006},
date = {2006-01-01},
journal = {Methods Enzymol},
volume = {415},
pages = {180-202},
abstract = {Crystal structures of complexes between ribosomal particles and antibiotics have pinned down very precisely the discrete binding sites of several classes of antibiotics inhibiting protein synthesis. The crystal structures of complexes between various antibiotics and ribosomal particles show definitively that ribosomal RNAs (rRNAs), rather than ribosomal proteins, are overwhelmingly targeted. The antibiotics are found at messenger RNA or transfer RNA binding sites and, most importantly, at pivot locations that are key for the structural rearrangements during the molecular mechanical steps in initiation, elongation, or termination of protein synthesis. We focus here on the 30S particle. Structurally, the antibiotics interact in many ways with RNA: (i) only with the phosphate groups (streptomycin); (ii) mainly with bases (hygromycin, spectinomycin); (iii) with a mixture of both (paromomycin, Geneticin); (iv) via magnesium ions (tetracycline) or a protein side chain (streptomycin). The antibiotics can mimic base stacking (pactamycin) or form pseudo-base pairing interactions with ribosomal bases (paromomycin and related aminoglycosides). Resistance strategies (mutations or methylations in rRNA or enzymatic modifications of the antibiotics) can generally be understood on the basis of the intermolecular contacts made between the antibiotics and rRNA residues in the crystal structures. In humans, toxicity of ribosomal antibiotics is most likely due, at least in part, to the sensitivity of mitochondrial ribosomes, since mitochondria evolved from a bacterial ancestor. Antibiotic families (e.g., aminoglycosides) form a set of invariant H-bonds to defined rRNA residues. When such residues are conserved in bacteria, but not in eukaryotes, resistance of eukaryotic ribosomes is observed. The structural knowledge, together with comparative genomic analysis, should allow for the development of new broad-spectrum antibiotics with higher selectivity toward bacterial ribosomes and less toxicity on eukaryotic cytoplasmic and mitochondrial ribosomes.},
note = {0076-6879 (Print)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Crystal structures of complexes between ribosomal particles and antibiotics have pinned down very precisely the discrete binding sites of several classes of antibiotics inhibiting protein synthesis. The crystal structures of complexes between various antibiotics and ribosomal particles show definitively that ribosomal RNAs (rRNAs), rather than ribosomal proteins, are overwhelmingly targeted. The antibiotics are found at messenger RNA or transfer RNA binding sites and, most importantly, at pivot locations that are key for the structural rearrangements during the molecular mechanical steps in initiation, elongation, or termination of protein synthesis. We focus here on the 30S particle. Structurally, the antibiotics interact in many ways with RNA: (i) only with the phosphate groups (streptomycin); (ii) mainly with bases (hygromycin, spectinomycin); (iii) with a mixture of both (paromomycin, Geneticin); (iv) via magnesium ions (tetracycline) or a protein side chain (streptomycin). The antibiotics can mimic base stacking (pactamycin) or form pseudo-base pairing interactions with ribosomal bases (paromomycin and related aminoglycosides). Resistance strategies (mutations or methylations in rRNA or enzymatic modifications of the antibiotics) can generally be understood on the basis of the intermolecular contacts made between the antibiotics and rRNA residues in the crystal structures. In humans, toxicity of ribosomal antibiotics is most likely due, at least in part, to the sensitivity of mitochondrial ribosomes, since mitochondria evolved from a bacterial ancestor. Antibiotic families (e.g., aminoglycosides) form a set of invariant H-bonds to defined rRNA residues. When such residues are conserved in bacteria, but not in eukaryotes, resistance of eukaryotic ribosomes is observed. The structural knowledge, together with comparative genomic analysis, should allow for the development of new broad-spectrum antibiotics with higher selectivity toward bacterial ribosomes and less toxicity on eukaryotic cytoplasmic and mitochondrial ribosomes.
Schuler M, Connell S R, Lescoute A, Giesebrecht J, Dabrowski M, Schroeer B, Mielke T, Penczek P A, Westhof E, Spahn C M
Structure of the ribosome-bound cricket paralysis virus IRES RNA Journal Article
In: Nat Struct Mol Biol, vol. 13, no. 12, pp. 1092-1096, 2006, ISBN: 17115051, (1545-9993 (Print) Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Structure of the ribosome-bound cricket paralysis virus IRES RNA},
author = {M Schuler and S R Connell and A Lescoute and J Giesebrecht and M Dabrowski and B Schroeer and T Mielke and P A Penczek and E Westhof and C M Spahn},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17115051},
isbn = {17115051},
year = {2006},
date = {2006-01-01},
journal = {Nat Struct Mol Biol},
volume = {13},
number = {12},
pages = {1092-1096},
abstract = {Internal ribosome entry sites (IRESs) facilitate an alternative, end-independent pathway of translation initiation. A particular family of dicistroviral IRESs can assemble elongation-competent 80S ribosomal complexes in the absence of canonical initiation factors and initiator transfer RNA. We present here a cryo-EM reconstruction of a dicistroviral IRES bound to the 80S ribosome. The resolution of the cryo-EM reconstruction, in the subnanometer range, allowed the molecular structure of the complete IRES in its active, ribosome-bound state to be solved. The structure, harboring three pseudoknot-containing domains, each with a specific functional role, shows how defined elements of the IRES emerge from a compactly folded core and interact with the key ribosomal components that form the A, P and E sites, where tRNAs normally bind. Our results exemplify the molecular strategy for recruitment of an IRES and reveal the dynamic features necessary for internal initiation.},
note = {1545-9993 (Print)
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Internal ribosome entry sites (IRESs) facilitate an alternative, end-independent pathway of translation initiation. A particular family of dicistroviral IRESs can assemble elongation-competent 80S ribosomal complexes in the absence of canonical initiation factors and initiator transfer RNA. We present here a cryo-EM reconstruction of a dicistroviral IRES bound to the 80S ribosome. The resolution of the cryo-EM reconstruction, in the subnanometer range, allowed the molecular structure of the complete IRES in its active, ribosome-bound state to be solved. The structure, harboring three pseudoknot-containing domains, each with a specific functional role, shows how defined elements of the IRES emerge from a compactly folded core and interact with the key ribosomal components that form the A, P and E sites, where tRNAs normally bind. Our results exemplify the molecular strategy for recruitment of an IRES and reveal the dynamic features necessary for internal initiation.
Leontis N B, Lescoute A, Westhof E
The building blocks and motifs of RNA architecture Journal Article
In: Curr Opin Struct Biol, vol. 16, no. 3, pp. 279-287, 2006, ISBN: 16713707, (0959-440X (Print) Journal Article Review).
Abstract | Links | BibTeX | Tags: ase Pairing Base Sequence Computational Biology/methods Conserved Sequence *Models, Extramural Research Support, Molecular Nucleic Acid Conformation RNA/*chemistry Research Support, N.I.H., Non-U.S. Gov't, Unité ARN, WESTHOF
@article{,
title = {The building blocks and motifs of RNA architecture},
author = {N B Leontis and A Lescoute and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16713707},
isbn = {16713707},
year = {2006},
date = {2006-01-01},
journal = {Curr Opin Struct Biol},
volume = {16},
number = {3},
pages = {279-287},
abstract = {RNA motifs can be defined broadly as recurrent structural elements containing multiple intramolecular RNA-RNA interactions, as observed in atomic-resolution RNA structures. They constitute the modular building blocks of RNA architecture, which is organized hierarchically. Recent work has focused on analyzing RNA backbone conformations to identify, define and search for new instances of recurrent motifs in X-ray structures. One current view asserts that recurrent RNA strand segments with characteristic backbone configurations qualify as independent motifs. Other considerations indicate that, to characterize modular motifs, one must take into account the larger structural context of such strand segments. This follows the biologically relevant motivation, which is to identify RNA structural characteristics that are subject to sequence constraints and that thus relate RNA architectures to sequences.},
note = {0959-440X (Print)
Journal Article
Review},
keywords = {ase Pairing Base Sequence Computational Biology/methods Conserved Sequence *Models, Extramural Research Support, Molecular Nucleic Acid Conformation RNA/*chemistry Research Support, N.I.H., Non-U.S. Gov't, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
RNA motifs can be defined broadly as recurrent structural elements containing multiple intramolecular RNA-RNA interactions, as observed in atomic-resolution RNA structures. They constitute the modular building blocks of RNA architecture, which is organized hierarchically. Recent work has focused on analyzing RNA backbone conformations to identify, define and search for new instances of recurrent motifs in X-ray structures. One current view asserts that recurrent RNA strand segments with characteristic backbone configurations qualify as independent motifs. Other considerations indicate that, to characterize modular motifs, one must take into account the larger structural context of such strand segments. This follows the biologically relevant motivation, which is to identify RNA structural characteristics that are subject to sequence constraints and that thus relate RNA architectures to sequences.
Lescoute A, Westhof E
The interaction networks of structured RNAs Journal Article
In: Nucleic Acids Res, vol. 34, no. 22, pp. 6587-6604, 2006, ISBN: 17135184, (1362-4962 (Electronic) Journal Article Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: 16S/chemistry RNA, 23S/chemistry Ribonuclease P/chemistry, Base Pairing Base Sequence Introns *Models, Catalytic/chemistry RNA, Molecular Molecular Sequence Data Nucleic Acid Conformation RNA/*chemistry RNA, Ribosomal, Unité ARN, WESTHOF
@article{,
title = {The interaction networks of structured RNAs},
author = {A Lescoute and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17135184},
isbn = {17135184},
year = {2006},
date = {2006-01-01},
journal = {Nucleic Acids Res},
volume = {34},
number = {22},
pages = {6587-6604},
abstract = {All pairwise interactions occurring between bases which could be detected in three-dimensional structures of crystallized RNA molecules are annotated on new planar diagrams. The diagrams attempt to map the underlying complex networks of base-base interactions and, especially, they aim at conveying key relationships between helical domains: co-axial stacking, bending and all Watson-Crick as well as non-Watson-Crick base pairs. Although such wiring diagrams cannot replace full stereographic images for correct spatial understanding and representation, they reveal structural similarities as well as the conserved patterns and distances between motifs which are present within the interaction networks of folded RNAs of similar or unrelated functions. Finally, the diagrams could help devising methods for meaningfully transforming RNA structures into graphs amenable to network analysis.},
note = {1362-4962 (Electronic)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {16S/chemistry RNA, 23S/chemistry Ribonuclease P/chemistry, Base Pairing Base Sequence Introns *Models, Catalytic/chemistry RNA, Molecular Molecular Sequence Data Nucleic Acid Conformation RNA/*chemistry RNA, Ribosomal, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
All pairwise interactions occurring between bases which could be detected in three-dimensional structures of crystallized RNA molecules are annotated on new planar diagrams. The diagrams attempt to map the underlying complex networks of base-base interactions and, especially, they aim at conveying key relationships between helical domains: co-axial stacking, bending and all Watson-Crick as well as non-Watson-Crick base pairs. Although such wiring diagrams cannot replace full stereographic images for correct spatial understanding and representation, they reveal structural similarities as well as the conserved patterns and distances between motifs which are present within the interaction networks of folded RNAs of similar or unrelated functions. Finally, the diagrams could help devising methods for meaningfully transforming RNA structures into graphs amenable to network analysis.
Westhof E
The ribosomal decoding site and antibiotics Journal Article
In: Biochimie, vol. 88, no. 8, pp. 931-933, 2006, ISBN: 16876930, (0300-9084 (Print) Editorial).
Links | BibTeX | Tags: Anti-Bacterial Agents/metabolism/*pharmacology Bacteria/*drug effects/genetics/growth & development Binding Sites/drug effects Protein Biosynthesis/drug effects/genetics RNA Amino Acyl/*metabolism, Bacterial/*metabolism RNA, Transfer, Unité ARN, WESTHOF
@article{,
title = {The ribosomal decoding site and antibiotics},
author = {E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16876930},
isbn = {16876930},
year = {2006},
date = {2006-01-01},
journal = {Biochimie},
volume = {88},
number = {8},
pages = {931-933},
note = {0300-9084 (Print)
Editorial},
keywords = {Anti-Bacterial Agents/metabolism/*pharmacology Bacteria/*drug effects/genetics/growth & development Binding Sites/drug effects Protein Biosynthesis/drug effects/genetics RNA Amino Acyl/*metabolism, Bacterial/*metabolism RNA, Transfer, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Lescoute A, Westhof E
Topology of three-way junctions in folded RNAs Journal Article
In: RNA, vol. 12, no. 1, pp. 83-93, 2006, ISBN: 16373494, (1355-8382 (Print) Journal Article).
Abstract | Links | BibTeX | Tags: Base Pairing Base Sequence *Crystallography Models, Molecular *Nucleic Acid Conformation RNA/*chemistry/ultrastructure, Unité ARN, WESTHOF
@article{,
title = {Topology of three-way junctions in folded RNAs},
author = {A Lescoute and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16373494},
isbn = {16373494},
year = {2006},
date = {2006-01-01},
journal = {RNA},
volume = {12},
number = {1},
pages = {83-93},
abstract = {The three-way junctions contained in X-ray structures of folded RNAs have been compiled and analyzed. Three-way junctions with two helices approximately coaxially stacked can be divided into three main families depending on the relative lengths of the segments linking the three Watson-Crick helices. Each family has topological characteristics with some conservation in the non-Watson-Crick pairs within the linking segments as well as in the types of contacts between the segments and the helices. The most populated family presents tertiary interactions between two helices as well as extensive shallow/minor groove contacts between a linking segment and the third helix. On the basis of the lengths of the linking segments, some guidelines could be deduced for choosing a topology for a three-way junction on the basis of a secondary structure. Examples and prediction bas'ed on those rules are discussed.},
note = {1355-8382 (Print)
Journal Article},
keywords = {Base Pairing Base Sequence *Crystallography Models, Molecular *Nucleic Acid Conformation RNA/*chemistry/ultrastructure, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The three-way junctions contained in X-ray structures of folded RNAs have been compiled and analyzed. Three-way junctions with two helices approximately coaxially stacked can be divided into three main families depending on the relative lengths of the segments linking the three Watson-Crick helices. Each family has topological characteristics with some conservation in the non-Watson-Crick pairs within the linking segments as well as in the types of contacts between the segments and the helices. The most populated family presents tertiary interactions between two helices as well as extensive shallow/minor groove contacts between a linking segment and the third helix. On the basis of the lengths of the linking segments, some guidelines could be deduced for choosing a topology for a three-way junction on the basis of a secondary structure. Examples and prediction bas'ed on those rules are discussed.
Kondo J, Urzhumtsev A, Westhof E
Two conformational states in the crystal structure of the Homo sapiens cytoplasmic ribosomal decoding A site Journal Article
In: Nucleic Acids Res, vol. 34, no. 2, pp. 676-685, 2006, ISBN: 16452297, (1362-4962 (Electronic) Journal Article).
Abstract | Links | BibTeX | Tags: 16S/chemistry RNA, 18S/*chemistry Research Support, Animals Comparative Study Crystallography, Bacterial/chemistry RNA, Molecular Nebramycin/analogs & derivatives/chemistry Nucleic Acid Conformation RNA, Non-U.S. Gov't Ribosomes/chemistry Tetrahymena thermophila/genetics, Protozoan/chemistry RNA, Ribosomal, Unité ARN, WESTHOF, X-Ray Genetic Code Humans *Models
@article{,
title = {Two conformational states in the crystal structure of the Homo sapiens cytoplasmic ribosomal decoding A site},
author = {J Kondo and A Urzhumtsev and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16452297},
isbn = {16452297},
year = {2006},
date = {2006-01-01},
journal = {Nucleic Acids Res},
volume = {34},
number = {2},
pages = {676-685},
abstract = {The decoding A site of the small ribosomal subunit is an RNA molecular switch, which monitors codon-anticodon interactions to guarantee translation fidelity. We have solved the crystal structure of an RNA fragment containing two Homo sapiens cytoplasmic A sites. Each of the two A sites presents a different conformational state. In one state, adenines A1492 and A1493 are fully bulged-out with C1409 forming a wobble-like pair to A1491. In the second state, adenines A1492 and A1493 form non-Watson-Crick pairs with C1409 and G1408, respectively while A1491 bulges out. The first state of the eukaryotic A site is, thus, basically the same as in the bacterial A site with bulging A1492 and A1493. It is the state used for recognition of the codon/anticodon complex. On the contrary, the second state of the H.sapiens cytoplasmic A site is drastically different from any of those observed for the bacterial A site without bulging A1492 and A1493.},
note = {1362-4962 (Electronic)
Journal Article},
keywords = {16S/chemistry RNA, 18S/*chemistry Research Support, Animals Comparative Study Crystallography, Bacterial/chemistry RNA, Molecular Nebramycin/analogs & derivatives/chemistry Nucleic Acid Conformation RNA, Non-U.S. Gov't Ribosomes/chemistry Tetrahymena thermophila/genetics, Protozoan/chemistry RNA, Ribosomal, Unité ARN, WESTHOF, X-Ray Genetic Code Humans *Models},
pubstate = {published},
tppubtype = {article}
}
The decoding A site of the small ribosomal subunit is an RNA molecular switch, which monitors codon-anticodon interactions to guarantee translation fidelity. We have solved the crystal structure of an RNA fragment containing two Homo sapiens cytoplasmic A sites. Each of the two A sites presents a different conformational state. In one state, adenines A1492 and A1493 are fully bulged-out with C1409 forming a wobble-like pair to A1491. In the second state, adenines A1492 and A1493 form non-Watson-Crick pairs with C1409 and G1408, respectively while A1491 bulges out. The first state of the eukaryotic A site is, thus, basically the same as in the bacterial A site with bulging A1492 and A1493. It is the state used for recognition of the codon/anticodon complex. On the contrary, the second state of the H.sapiens cytoplasmic A site is drastically different from any of those observed for the bacterial A site without bulging A1492 and A1493.
2005
Westhof E, Vicens Q
Crystallographic Studies of Complexes between the Ribosomal Decoding Site and Aminoglycosides Antibiotics Book Chapter
In: Niimura, N; Mizuno, H; Helliwell, J; Westhof, E (Ed.): Hydrogen- and Hydration-Sensitive Structural Biology, pp. 125-133, KubaPro Co. Ltd., 2005.
Links | BibTeX | Tags: Unité ARN, WESTHOF
@inbook{,
title = {Crystallographic Studies of Complexes between the Ribosomal Decoding Site and Aminoglycosides Antibiotics},
author = {E Westhof and Q Vicens},
editor = {N Niimura and H Mizuno and J Helliwell and E Westhof},
url = {http://pure.au.dk/portal/en/publications/crystallographic-studies-of-complexes-between-the-ribosomal-decoding-site-and-aminoglycoside-antibiotics%284a6ee78e-3d0a-43ba-9f46-4bdebbe3eb51%29.html},
year = {2005},
date = {2005-01-01},
booktitle = {Hydrogen- and Hydration-Sensitive Structural Biology},
pages = {125-133},
publisher = {KubaPro Co. Ltd.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {inbook}
}
Westhof E, Patel D J
Nucleic acids RNA: from architecture to recognition and catalysis Journal Article
In: Curr Opin Struct Biol, vol. 15, no. 3, pp. 309-312, 2005, ISBN: 15922589, (0959-440x Editorial).
Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Nucleic acids RNA: from architecture to recognition and catalysis},
author = {E Westhof and D J Patel},
url = {http://www-ibmc.u-strasbg.fr/upr9002/westhof/PDF/r2005_EWesthof_COSB.pdf},
isbn = {15922589},
year = {2005},
date = {2005-01-01},
journal = {Curr Opin Struct Biol},
volume = {15},
number = {3},
pages = {309-312},
note = {0959-440x
Editorial},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Westhof E
Muttaiya Sundaralingam (1931-2004): A Pioneering Stereochemist and Crystallographer of Nucleic Acids Journal Article
In: Structure, vol. 13, no. 3, pp. 343345, 2005.
Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Muttaiya Sundaralingam (1931-2004): A Pioneering Stereochemist and Crystallographer of Nucleic Acids},
author = {E Westhof},
url = {http://www.sciencedirect.com/science/article/pii/S0969212605000870},
doi = {10.1016/j.str.2005.02.009},
year = {2005},
date = {2005-01-01},
journal = {Structure},
volume = {13},
number = {3},
pages = {343345},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Westhof E
Molecular recognition between the ribosomal decoding site and natural or non-natural aminoglycosides Journal Article
In: Nucleic Acids Symp Ser, no. 49, pp. 59-60, 2005, ISBN: 17150632, (1746-8272 (Electronic) Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Molecular recognition between the ribosomal decoding site and natural or non-natural aminoglycosides},
author = {E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17150632},
isbn = {17150632},
year = {2005},
date = {2005-01-01},
journal = {Nucleic Acids Symp Ser},
number = {49},
pages = {59-60},
abstract = {Crystal structures of complexes between ribosomal particles and antibiotics have pinned down very precisely the discrete binding sites of several classes of antibiotics inhibiting protein synthesis. The crystal structures of complexes between various antibiotics and ribosomal particles show definitively that ribosomal RNAs, rather than ribosomal proteins, are overwhelmingly targeted. The comparative analysis of various aminoglycosides bound to the same site has been used to decipher the contribution of each functional group to the RNA/aminoglycoside complex and to attempt to rationalize various biochemical and microbiological data as well as some resistance and toxicity mechanisms at the molecular level. Tight packing of atoms in direct van der Waals contact is central and a prerequisite to specific recognition. Water molecules participate in the assembly by linking hydrophilic groups belonging to both components. The hydration shells around nucleic acid base pairs tend to be conserved and maintained whatever the environment. Two regions are crucial for specificity and resistance: A1408 and the non-Watson-Crick pair U1406-U1495.},
note = {1746-8272 (Electronic)
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Crystal structures of complexes between ribosomal particles and antibiotics have pinned down very precisely the discrete binding sites of several classes of antibiotics inhibiting protein synthesis. The crystal structures of complexes between various antibiotics and ribosomal particles show definitively that ribosomal RNAs, rather than ribosomal proteins, are overwhelmingly targeted. The comparative analysis of various aminoglycosides bound to the same site has been used to decipher the contribution of each functional group to the RNA/aminoglycoside complex and to attempt to rationalize various biochemical and microbiological data as well as some resistance and toxicity mechanisms at the molecular level. Tight packing of atoms in direct van der Waals contact is central and a prerequisite to specific recognition. Water molecules participate in the assembly by linking hydrophilic groups belonging to both components. The hydration shells around nucleic acid base pairs tend to be conserved and maintained whatever the environment. Two regions are crucial for specificity and resistance: A1408 and the non-Watson-Crick pair U1406-U1495.
Przybilski R, Graf S, Lescoute A, Nellen W, Westhof E, Steger G, Hammann C
Functional Hammerhead Ribozymes Naturally Encoded in the Genome of Arabidopsis thaliana Journal Article
In: Plant Cell, vol. 17, no. 7, pp. 1877-1885, 2005, ISBN: 15937227, (1040-4651 Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Functional Hammerhead Ribozymes Naturally Encoded in the Genome of Arabidopsis thaliana},
author = {R Przybilski and S Graf and A Lescoute and W Nellen and E Westhof and G Steger and C Hammann},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15937227},
isbn = {15937227},
year = {2005},
date = {2005-01-01},
journal = {Plant Cell},
volume = {17},
number = {7},
pages = {1877-1885},
abstract = {The hammerhead ribozyme (HHRz) is an autocatalytic RNA motif found in subviral plant pathogens and transcripts of repetitive DNA sequences in animals. Here, we report the discovery and characterization of unique HHRzs encoded in a plant genome. Two novel sequences were identified on chromosome IV of Arabidopsis thaliana in a database search, which took into account recently defined structural requirements. The HHRzs are expressed in several tissues and coexist in vivo as both cleaved and noncleaved species. In vitro, both sequences cleave efficiently at physiological Mg(2+) concentrations, indicative of functional loop-loop interactions. Kinetic analysis of loop nucleotide variants was used to determine a three-dimensional model of these tertiary interactions. Based on these results, on the lack of infectivity of hammerhead-carrying viroids in Arabidopsis, and on extensive sequence comparisons, we propose that the ribozyme sequences did not invade this plant by horizontal transfer but have evolved independently to perform a specific, yet unidentified, biological function.},
note = {1040-4651
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The hammerhead ribozyme (HHRz) is an autocatalytic RNA motif found in subviral plant pathogens and transcripts of repetitive DNA sequences in animals. Here, we report the discovery and characterization of unique HHRzs encoded in a plant genome. Two novel sequences were identified on chromosome IV of Arabidopsis thaliana in a database search, which took into account recently defined structural requirements. The HHRzs are expressed in several tissues and coexist in vivo as both cleaved and noncleaved species. In vitro, both sequences cleave efficiently at physiological Mg(2+) concentrations, indicative of functional loop-loop interactions. Kinetic analysis of loop nucleotide variants was used to determine a three-dimensional model of these tertiary interactions. Based on these results, on the lack of infectivity of hammerhead-carrying viroids in Arabidopsis, and on extensive sequence comparisons, we propose that the ribozyme sequences did not invade this plant by horizontal transfer but have evolved independently to perform a specific, yet unidentified, biological function.
Pfister P, Hobbie S, Brull C, Corti N, Vasella A, Westhof E, Bottger E C
Mutagenesis of 16S rRNA C1409-G1491 base-pair differentiates between 6'OH and 6'NH3+ aminoglycosides Journal Article
In: J Mol Biol, vol. 346, no. 2, pp. 467-475, 2005, ISBN: 15670597, (0022-2836 Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Mutagenesis of 16S rRNA C1409-G1491 base-pair differentiates between 6'OH and 6'NH3+ aminoglycosides},
author = {P Pfister and S Hobbie and C Brull and N Corti and A Vasella and E Westhof and E C Bottger},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15670597},
isbn = {15670597},
year = {2005},
date = {2005-01-01},
journal = {J Mol Biol},
volume = {346},
number = {2},
pages = {467-475},
abstract = {Using a single rRNA allelic Gram-positive model system, we systematically mutagenized 16S rRNA positions 1409 and 1491 to probe the functional relevance of structural interactions between aminoglycoside antibiotics and the A-site rRNA that were suggested by X-ray crystallography. At the structural level, the interaction of the 2-deoxystreptamine aminoglycosides with the rRNA base-pair C1409-G1491 has been suggested to involve the following features: (i) ring I of the disubstituted 2-deoxystreptamines stacks upon G1491 and H-bonds to the Watson-Crick edge of A1408; (ii) ring III of the 4,5-disubstituted aminoglycosides shows hydrogen bonding to G1491. However, we found that mutants with altered 16S rRNA bases 1409 and 1491 discriminated poorly between 4,5-disubstituted and 4,6-disubstituted 2-deoxystreptamines, but differentially affected aminoglycosides with a hydroxyl group versus an ammonium group at position 6' of ring I, e.g. G1491U conferred high-level drug resistance to paromomycin and geneticin, but not to neomycin, tobramycin or gentamicin.},
note = {0022-2836
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Using a single rRNA allelic Gram-positive model system, we systematically mutagenized 16S rRNA positions 1409 and 1491 to probe the functional relevance of structural interactions between aminoglycoside antibiotics and the A-site rRNA that were suggested by X-ray crystallography. At the structural level, the interaction of the 2-deoxystreptamine aminoglycosides with the rRNA base-pair C1409-G1491 has been suggested to involve the following features: (i) ring I of the disubstituted 2-deoxystreptamines stacks upon G1491 and H-bonds to the Watson-Crick edge of A1408; (ii) ring III of the 4,5-disubstituted aminoglycosides shows hydrogen bonding to G1491. However, we found that mutants with altered 16S rRNA bases 1409 and 1491 discriminated poorly between 4,5-disubstituted and 4,6-disubstituted 2-deoxystreptamines, but differentially affected aminoglycosides with a hydroxyl group versus an ammonium group at position 6' of ring I, e.g. G1491U conferred high-level drug resistance to paromomycin and geneticin, but not to neomycin, tobramycin or gentamicin.
Lescoute A, Westhof E
Riboswitch structures: purine ligands replace tertiary contacts Journal Article
In: Chem Biol, vol. 12, no. 1, pp. 10-13, 2005, ISBN: 15664510, (1074-5521 Journal Article).
Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Riboswitch structures: purine ligands replace tertiary contacts},
author = {A Lescoute and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15664510},
isbn = {15664510},
year = {2005},
date = {2005-01-01},
journal = {Chem Biol},
volume = {12},
number = {1},
pages = {10-13},
note = {1074-5521
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Kondo J, Francois B, Urzhumtsev A, Westhof E
Crystallographic studies of Homo sapiens ribosomal decoding A site complexed with aminoglycosides Journal Article
In: Nucleic Acids Symp Ser, vol. 49, no. 1, pp. 253-254, 2005.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Crystallographic studies of Homo sapiens ribosomal decoding A site complexed with aminoglycosides},
author = {J Kondo and B Francois and A Urzhumtsev and E Westhof},
url = {http://nass.oxfordjournals.org/content/49/1/253.abstract},
year = {2005},
date = {2005-01-01},
journal = {Nucleic Acids Symp Ser},
volume = {49},
number = {1},
pages = {253-254},
abstract = {Aminoglycosides are highly effective antibacterial drugs that decrease translation accuracy by binding to the aminoacyl-tRNA decoding site (A site) of 16S ribosomal RNA. On the other hand, they are highly toxic to mammals through kidney and ear-associated illnesses by binding to ribosomal A sites. To understand the mechanism of toxicity of aminoglycosides to mammals at atomic level, crystallographic studies have been carried out with a number of Homo sapiens mitochondrial and cytoplasmic A sites complexed with aminoglycosides. Several X-ray diffraction data sets were successfully collected. Initial phases of mitochondrial A site with tobramycin and cytoplasmic A site with paromomycin were derived by the molecular replacement method. Refinements of atomic parameters are now under progress.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Aminoglycosides are highly effective antibacterial drugs that decrease translation accuracy by binding to the aminoacyl-tRNA decoding site (A site) of 16S ribosomal RNA. On the other hand, they are highly toxic to mammals through kidney and ear-associated illnesses by binding to ribosomal A sites. To understand the mechanism of toxicity of aminoglycosides to mammals at atomic level, crystallographic studies have been carried out with a number of Homo sapiens mitochondrial and cytoplasmic A sites complexed with aminoglycosides. Several X-ray diffraction data sets were successfully collected. Initial phases of mitochondrial A site with tobramycin and cytoplasmic A site with paromomycin were derived by the molecular replacement method. Refinements of atomic parameters are now under progress.
Jossinet F, Westhof E
Sequence to Structure (S2S): display, manipulate and interconnect RNA data from sequence to structure Journal Article
In: Bioinformatics, vol. 21, no. 15, pp. 3320-3321, 2005, ISBN: 15905274, (1367-4803 Journal article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Sequence to Structure (S2S): display, manipulate and interconnect RNA data from sequence to structure},
author = {F Jossinet and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15905274},
isbn = {15905274},
year = {2005},
date = {2005-01-01},
journal = {Bioinformatics},
volume = {21},
number = {15},
pages = {3320-3321},
abstract = {SUMMARY: Efficient RNA sequence manipulations (like multiple alignments) need to be constrained by rules of RNA structure folding. The structural knowledge has increased dramatically in the last years with the accumulation of several large RNA structures like those of the bacterial ribosome subunits. However, no tool in the RNA community provides an easy way to link and integrate progress made at the sequence level using the available three-dimensional information. S2S proposes a framework in which an user can easily display, manipulate, and interconnect heterogeneous RNA data like multiple sequence alignments, secondary and tertiary structures. S2S has been implemented with the Java language and has been developed and tested under UNIX systems like Linux and MacOSX. AVAILABILITY: S2S is available at http://bioinformatics.org/S2S/.},
note = {1367-4803
Journal article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
SUMMARY: Efficient RNA sequence manipulations (like multiple alignments) need to be constrained by rules of RNA structure folding. The structural knowledge has increased dramatically in the last years with the accumulation of several large RNA structures like those of the bacterial ribosome subunits. However, no tool in the RNA community provides an easy way to link and integrate progress made at the sequence level using the available three-dimensional information. S2S proposes a framework in which an user can easily display, manipulate, and interconnect heterogeneous RNA data like multiple sequence alignments, secondary and tertiary structures. S2S has been implemented with the Java language and has been developed and tested under UNIX systems like Linux and MacOSX. AVAILABILITY: S2S is available at http://bioinformatics.org/S2S/.
Fritsch V, Westhof E
Introduction to non-watson-crick base pairs and RNA folding Book Chapter
In: Chatenay, D; Cocco, S; Monasson, R; Thieffry, D; Dalibard, J (Ed.): Multiple aspects of DNA: from Biophysics to Bioinformatics. Lecture Notes of the Les Houches Summer School 2004, vol. 82, pp. 41-72, Elsevier, 2005.
Links | BibTeX | Tags: Unité ARN, WESTHOF
@inbook{,
title = {Introduction to non-watson-crick base pairs and RNA folding},
author = {V Fritsch and E Westhof},
editor = {D Chatenay and S Cocco and R Monasson and D Thieffry and J Dalibard},
url = {http://www.sciencedirect.com/science/article/pii/S0924809905800290},
doi = {10.1016/S0924-8099(05)80029-0},
year = {2005},
date = {2005-01-01},
booktitle = {Multiple aspects of DNA: from Biophysics to Bioinformatics. Lecture Notes of the Les Houches Summer School 2004},
volume = {82},
pages = {41-72},
publisher = {Elsevier},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {inbook}
}
Chaloin O, Peter J C, Briand J P, Masquida B, Desgranges C, Muller S, Hoebeke J
The N-terminus of HIV-1 Tat protein is essential for Tat-TAR RNA interaction Journal Article
In: Cell Mol Life Sci, vol. 62, no. 3, pp. 355-361, 2005, ISBN: 15723170, (1420-682x Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {The N-terminus of HIV-1 Tat protein is essential for Tat-TAR RNA interaction},
author = {O Chaloin and J C Peter and J P Briand and B Masquida and C Desgranges and S Muller and J Hoebeke},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15723170},
isbn = {15723170},
year = {2005},
date = {2005-01-01},
journal = {Cell Mol Life Sci},
volume = {62},
number = {3},
pages = {355-361},
abstract = {The human HIV transactivator protein Tat is essential for efficient viral transcription that occurs by a complex mechanism involving interaction of Tat with the TAR RNA element. This interaction appears to require the mediation of a cellular protein, cyclin T1. However, the possibility that Tat and TAR associate in a binary Tat-TAR complex has been little investigated. Using a chemically synthesized active Tat protein, the kinetic and equilibrium parameters of its interaction with TAR were determined by surface plasmon resonance technology. Independently of partner and method of immobilization onto the sensor chip, the association (k(a) = 5-9 x 105 M(-1) s(-1)) and dissociation rate constants (k(d) = 1.7-4.3 x 10(-3) s(-1)) yielded similar equilibrium dissociation constants (K(d) = 2-8 nM). A truncated peptide encompassing residues 30-86 of Tat did not bind to TAR at all. We conclude that Tat can form a high-affinity complex with TAR in the absence of cyclin T1 and that the N-terminal domain of Tat is essential for this interaction, suggesting a conformational link between this domain and the basic domain of Tat. These results are important in our quest for developing therapeutic compounds that impair viral replication.},
note = {1420-682x
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The human HIV transactivator protein Tat is essential for efficient viral transcription that occurs by a complex mechanism involving interaction of Tat with the TAR RNA element. This interaction appears to require the mediation of a cellular protein, cyclin T1. However, the possibility that Tat and TAR associate in a binary Tat-TAR complex has been little investigated. Using a chemically synthesized active Tat protein, the kinetic and equilibrium parameters of its interaction with TAR were determined by surface plasmon resonance technology. Independently of partner and method of immobilization onto the sensor chip, the association (k(a) = 5-9 x 105 M(-1) s(-1)) and dissociation rate constants (k(d) = 1.7-4.3 x 10(-3) s(-1)) yielded similar equilibrium dissociation constants (K(d) = 2-8 nM). A truncated peptide encompassing residues 30-86 of Tat did not bind to TAR at all. We conclude that Tat can form a high-affinity complex with TAR in the absence of cyclin T1 and that the N-terminal domain of Tat is essential for this interaction, suggesting a conformational link between this domain and the basic domain of Tat. These results are important in our quest for developing therapeutic compounds that impair viral replication.
Baird N J, Westhof E, Qin H, Pan T, Sosnick T R
Structure of a Folding Intermediate Reveals the Interplay Between Core and Peripheral Elements in RNA Folding Journal Article
In: J Mol Biol, vol. 352, no. 3, pp. 712-722, 2005, ISBN: 16115647, (0022-2836 Journal article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Structure of a Folding Intermediate Reveals the Interplay Between Core and Peripheral Elements in RNA Folding},
author = {N J Baird and E Westhof and H Qin and T Pan and T R Sosnick},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16115647},
isbn = {16115647},
year = {2005},
date = {2005-01-01},
journal = {J Mol Biol},
volume = {352},
number = {3},
pages = {712-722},
abstract = {Though the molecular architecture of many native RNA structures has been characterized, the structures of folding intermediates are poorly defined. Here, we present a nucleotide-level model of a highly structured equilibrium folding intermediate of the specificity domain of the Bacillus subtilis RNase P RNA, obtained using chemical and nuclease mapping, circular dichroism spectroscopy, small-angle X-ray scattering and molecular modeling. The crystal structure indicates that the 154 nucleotide specificity domain is composed of several secondary and tertiary structural modules. The structure of the intermediate contains modules composed of secondary structures and short-range tertiary interactions, implying a sequential order of tertiary structure formation during folding. The intermediate lacks the native core and several long-range interactions among peripheral regions, such as a GAAA tetraloop and its receptor. Folding to the native structure requires the local rearrangement of a T-loop in the core in concert with the formation of the GAAA tetraloop-receptor interaction. The interplay of core and peripheral structure formation rationalizes the high degree of cooperativity observed in the folding transition leading to the native structure.},
note = {0022-2836
Journal article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Though the molecular architecture of many native RNA structures has been characterized, the structures of folding intermediates are poorly defined. Here, we present a nucleotide-level model of a highly structured equilibrium folding intermediate of the specificity domain of the Bacillus subtilis RNase P RNA, obtained using chemical and nuclease mapping, circular dichroism spectroscopy, small-angle X-ray scattering and molecular modeling. The crystal structure indicates that the 154 nucleotide specificity domain is composed of several secondary and tertiary structural modules. The structure of the intermediate contains modules composed of secondary structures and short-range tertiary interactions, implying a sequential order of tertiary structure formation during folding. The intermediate lacks the native core and several long-range interactions among peripheral regions, such as a GAAA tetraloop and its receptor. Folding to the native structure requires the local rearrangement of a T-loop in the core in concert with the formation of the GAAA tetraloop-receptor interaction. The interplay of core and peripheral structure formation rationalizes the high degree of cooperativity observed in the folding transition leading to the native structure.
Kachouri R, Stribinskis V, Zhu Y, Ramos K S, Westhof E, Li Y
A surprisingly large RNase P RNA in Candida glabrata Journal Article
In: RNA, vol. 11, no. 7, pp. 1064-1072, 2005, ISBN: 15987816, (1355-8382 Journal Article).
Abstract | Links | BibTeX | Tags: Ascomycota/classification/genetics Base Sequence Candida glabrata/chemistry/*enzymology/genetics/*metabolism Comparative Study Conserved Sequence DNA, Chemical Molecular Sequence Data Mutation Nucleic Acid Conformation Phylogeny RNA, Fungal Databases, Fungal Genome, Fungal Models, Fungal/*chemistry/genetics/isolation & purification/metabolism Research Support, Genetic Genes, Non-U.S. Gov't Ribonuclease P/*chemistry/genetics/metabolism Sequence Homology, Nucleic Acid Variation (Genetics), Unité ARN, WESTHOF
@article{,
title = {A surprisingly large RNase P RNA in Candida glabrata},
author = {R Kachouri and V Stribinskis and Y Zhu and K S Ramos and E Westhof and Y Li},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15987816},
isbn = {15987816},
year = {2005},
date = {2005-01-01},
journal = {RNA},
volume = {11},
number = {7},
pages = {1064-1072},
abstract = {We have found an extremely large ribonuclease P (RNase P) RNA (RPR1) in the human pathogen Candida glabrata and verified that this molecule is expressed and present in the active enzyme complex of this hemiascomycete yeast. A structural alignment of the C. glabrata sequence with 36 other hemiascomycete RNase P RNAs (abbreviated as P RNAs) allows us to characterize the types of insertions. In addition, 15 P RNA sequences were newly characterized by searching in the recently sequenced genomes Candida albicans, C. glabrata, Debaryomyces hansenii, Eremothecium gossypii, Kluyveromyces lactis, Kluyveromyces waltii, Naumovia castellii, Saccharomyces kudriavzevii, Saccharomyces mikatae, and Yarrowia lipolytica; and by PCR amplification for other Candida species (Candida guilliermondii, Candida krusei, Candida parapsilosis, Candida stellatoidea, and Candida tropicalis). The phylogenetic comparative analysis identifies a hemiascomycete secondary structure consensus that presents a conserved core in all species with variable insertions or deletions. The most significant variability is found in C. glabrata P RNA in which three insertions exceeding in total 700 nt are present in the Specificity domain. This P RNA is more than twice the length of any other homologous P RNAs known in the three domains of life and is eight times the size of the smallest. RNase P RNA, therefore, represents one of the most diversified noncoding RNAs in terms of size variation and structural diversity.},
note = {1355-8382
Journal Article},
keywords = {Ascomycota/classification/genetics Base Sequence Candida glabrata/chemistry/*enzymology/genetics/*metabolism Comparative Study Conserved Sequence DNA, Chemical Molecular Sequence Data Mutation Nucleic Acid Conformation Phylogeny RNA, Fungal Databases, Fungal Genome, Fungal Models, Fungal/*chemistry/genetics/isolation & purification/metabolism Research Support, Genetic Genes, Non-U.S. Gov't Ribonuclease P/*chemistry/genetics/metabolism Sequence Homology, Nucleic Acid Variation (Genetics), Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
We have found an extremely large ribonuclease P (RNase P) RNA (RPR1) in the human pathogen Candida glabrata and verified that this molecule is expressed and present in the active enzyme complex of this hemiascomycete yeast. A structural alignment of the C. glabrata sequence with 36 other hemiascomycete RNase P RNAs (abbreviated as P RNAs) allows us to characterize the types of insertions. In addition, 15 P RNA sequences were newly characterized by searching in the recently sequenced genomes Candida albicans, C. glabrata, Debaryomyces hansenii, Eremothecium gossypii, Kluyveromyces lactis, Kluyveromyces waltii, Naumovia castellii, Saccharomyces kudriavzevii, Saccharomyces mikatae, and Yarrowia lipolytica; and by PCR amplification for other Candida species (Candida guilliermondii, Candida krusei, Candida parapsilosis, Candida stellatoidea, and Candida tropicalis). The phylogenetic comparative analysis identifies a hemiascomycete secondary structure consensus that presents a conserved core in all species with variable insertions or deletions. The most significant variability is found in C. glabrata P RNA in which three insertions exceeding in total 700 nt are present in the Specificity domain. This P RNA is more than twice the length of any other homologous P RNAs known in the three domains of life and is eight times the size of the smallest. RNase P RNA, therefore, represents one of the most diversified noncoding RNAs in terms of size variation and structural diversity.
Nielsen H, Westhof E, Johansen S
An mRNA is capped by a 2', 5' lariat catalyzed by a group I-like ribozyme Journal Article
In: Science, vol. 309, no. 5740, pp. 1584-1587, 2005, ISBN: 16141078, (1095-9203 (Electronic) Journal Article).
Abstract | Links | BibTeX | Tags: ase Sequence Catalysis Endonucleases/biosynthesis/*genetics Esterification *Introns Molecular Sequence Data RNA Caps/*chemistry *RNA Splicing RNA, Catalytic/chemistry/*metabolism Research Support, Non-U.S. Gov't, Unité ARN, WESTHOF
@article{,
title = {An mRNA is capped by a 2', 5' lariat catalyzed by a group I-like ribozyme},
author = {H Nielsen and E Westhof and S Johansen},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16141078},
isbn = {16141078},
year = {2005},
date = {2005-01-01},
journal = {Science},
volume = {309},
number = {5740},
pages = {1584-1587},
abstract = {Twin-ribozyme introns are formed by two ribozymes belonging to the group I family and occur in some ribosomal RNA transcripts. The group I-like ribozyme, GIR1, liberates the 5' end of a homing endonuclease messenger RNA in the slime mold Didymium iridis. We demonstrate that this cleavage occurs by a transesterification reaction with the joining of the first and the third nucleotide of the messenger by a 2',5'-phosphodiester linkage. Thus, a group I-like ribozyme catalyzes an RNA branching reaction similar to the first step of splicing in group II introns and spliceosomal introns. The resulting short lariat, by forming a protective 5' cap, might have been useful in a primitive RNA world.},
note = {1095-9203 (Electronic)
Journal Article},
keywords = {ase Sequence Catalysis Endonucleases/biosynthesis/*genetics Esterification *Introns Molecular Sequence Data RNA Caps/*chemistry *RNA Splicing RNA, Catalytic/chemistry/*metabolism Research Support, Non-U.S. Gov't, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Twin-ribozyme introns are formed by two ribozymes belonging to the group I family and occur in some ribosomal RNA transcripts. The group I-like ribozyme, GIR1, liberates the 5' end of a homing endonuclease messenger RNA in the slime mold Didymium iridis. We demonstrate that this cleavage occurs by a transesterification reaction with the joining of the first and the third nucleotide of the messenger by a 2',5'-phosphodiester linkage. Thus, a group I-like ribozyme catalyzes an RNA branching reaction similar to the first step of splicing in group II introns and spliceosomal introns. The resulting short lariat, by forming a protective 5' cap, might have been useful in a primitive RNA world.
Hobbie S N, Pfister P, Brull C, Westhof E, Bottger E C
Analysis of the contribution of individual substituents in 4,6-aminoglycoside-ribosome interaction Journal Article
In: Antimicrob Agents Chemother, vol. 49, no. 12, pp. 5112-5118, 2005, ISBN: 16304180, (0066-4804 (Print) Journal Article).
Abstract | Links | BibTeX | Tags: Aminoglycosides/chemistry/*pharmacology Anti-Bacterial Agents/chemistry/*pharmacology Binding Sites DNA, Bacterial/genetics Drug Design Mutation Mycobacterium smegmatis/*drug effects/genetics/metabolism RNA, Bacterial/genetics Research Support, Non-U.S. Gov't Ribosomes/chemistry/drug effects/*metabolism Structure-Activity Relationship, Unité ARN, WESTHOF
@article{,
title = {Analysis of the contribution of individual substituents in 4,6-aminoglycoside-ribosome interaction},
author = {S N Hobbie and P Pfister and C Brull and E Westhof and E C Bottger},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16304180},
isbn = {16304180},
year = {2005},
date = {2005-01-01},
journal = {Antimicrob Agents Chemother},
volume = {49},
number = {12},
pages = {5112-5118},
abstract = {The 4,6-disubstituted 2-deoxystreptamines interfere with protein biosynthesis by specifically targeting the ribosomal A site. These drugs show subtle variations in the chemical groups of rings I, II, and III. In the present study we used site-directed mutagenesis to generate mutant strains of Mycobacterium smegmatis mc(2)155 SMR5 DeltarrnB with mutations in its single rRNA allele, rrnA. This genetic procedure gives rise to strains carrying homogeneous populations of mutant ribosomes and was used to study the contribution of individual chemical substituents to the binding of 4,6-disubstituted aminoglycosides. X-ray crystal structures of geneticin and tobramycin complexed to oligonucleotides containing the minimal bacterial ribosomal A site were used for interpretation of MICs determined for a panel of 4,6-aminoglycosides, including tobramycin, kanamycin A, kanamycin B, amikacin, gentamicin, and geneticin. Surprisingly, the considerable differences present within ring III did not seem to alter the interaction of the drug with the ribosome, as determined by site-directed mutagenesis of the A site. In contrast, subtle variations in ring I significantly influenced binding: (i) a 4'-hydroxyl moiety participates in the proper drug target interaction; and (ii) a 2'-amino group contributes an additional positive charge to ring I, making the drug less susceptible to any kind of sequence alteration within the decoding site, most notably, to conformational changes induced by transversion of U1495 to 1495A. The 4-amino-2-hydroxyl-1-oxobutyl extension at position 1 of ring II of amikacin provides an additional anchor and renders amikacin less dependent on the structural conformation of nucleotide U1406 compared to the dependencies of other kanamycins. Overall, the set of interactions forming the complex between drug substituents and nucleotides of the A site constitutes a network in which the interactions can partly compensate for each other when they are disrupted.},
note = {0066-4804 (Print)
Journal Article},
keywords = {Aminoglycosides/chemistry/*pharmacology Anti-Bacterial Agents/chemistry/*pharmacology Binding Sites DNA, Bacterial/genetics Drug Design Mutation Mycobacterium smegmatis/*drug effects/genetics/metabolism RNA, Bacterial/genetics Research Support, Non-U.S. Gov't Ribosomes/chemistry/drug effects/*metabolism Structure-Activity Relationship, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The 4,6-disubstituted 2-deoxystreptamines interfere with protein biosynthesis by specifically targeting the ribosomal A site. These drugs show subtle variations in the chemical groups of rings I, II, and III. In the present study we used site-directed mutagenesis to generate mutant strains of Mycobacterium smegmatis mc(2)155 SMR5 DeltarrnB with mutations in its single rRNA allele, rrnA. This genetic procedure gives rise to strains carrying homogeneous populations of mutant ribosomes and was used to study the contribution of individual chemical substituents to the binding of 4,6-disubstituted aminoglycosides. X-ray crystal structures of geneticin and tobramycin complexed to oligonucleotides containing the minimal bacterial ribosomal A site were used for interpretation of MICs determined for a panel of 4,6-aminoglycosides, including tobramycin, kanamycin A, kanamycin B, amikacin, gentamicin, and geneticin. Surprisingly, the considerable differences present within ring III did not seem to alter the interaction of the drug with the ribosome, as determined by site-directed mutagenesis of the A site. In contrast, subtle variations in ring I significantly influenced binding: (i) a 4'-hydroxyl moiety participates in the proper drug target interaction; and (ii) a 2'-amino group contributes an additional positive charge to ring I, making the drug less susceptible to any kind of sequence alteration within the decoding site, most notably, to conformational changes induced by transversion of U1495 to 1495A. The 4-amino-2-hydroxyl-1-oxobutyl extension at position 1 of ring II of amikacin provides an additional anchor and renders amikacin less dependent on the structural conformation of nucleotide U1406 compared to the dependencies of other kanamycins. Overall, the set of interactions forming the complex between drug substituents and nucleotides of the A site constitutes a network in which the interactions can partly compensate for each other when they are disrupted.
Kisseleva N, Khvorova A, Westhof E, Schiemann O
Binding of manganese(II) to a tertiary stabilized hammerhead ribozyme as studied by electron paramagnetic resonance spectroscopy Journal Article
In: RNA, vol. 11, no. 1, pp. 1-6, 2005, ISBN: 15611296, (1355-8382 Letter).
Abstract | Links | BibTeX | Tags: Base Sequence Binding Sites Electron Spin Resonance Spectroscopy Framycetin/chemistry/metabolism Kinetics Manganese/*metabolism Nucleic Acid Conformation RNA, Catalytic/*chemistry/*metabolism Research Support, Non-U.S. Gov't, Unité ARN, WESTHOF
@article{,
title = {Binding of manganese(II) to a tertiary stabilized hammerhead ribozyme as studied by electron paramagnetic resonance spectroscopy},
author = {N Kisseleva and A Khvorova and E Westhof and O Schiemann},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15611296},
isbn = {15611296},
year = {2005},
date = {2005-01-01},
journal = {RNA},
volume = {11},
number = {1},
pages = {1-6},
abstract = {Electron paramagnetic resonance (EPR) spectroscopy is used to study the binding of MnII ions to a tertiary stabilized hammer-head ribozyme (tsHHRz) and to compare it with the binding to the minimal hammerhead ribozyme (mHHRz). Continuous wave EPR measurements show that the tsHHRz possesses a single high-affinity MnII binding site with a KD of < or =10 nM at an NaCl concentration of 0.1 M. This dissociation constant is at least two orders of magnitude smaller than the KD determined previously for the single high-affinity MnII site in the mHHRz. In addition, whereas the high-affinity MnII is displaced from the mHHRz upon binding of the aminoglycoside antibiotic neomycin B, it is not from the tsHHRz. Despite these pronounced differences in binding, a comparison between the electron spin echo envelope modulation and hyperfine sublevel correlation spectra of the minimal and tertiary stabilized HHRz demonstrates that the structure of both binding sites is very similar. This suggests that the MnII is located in both ribozymes between the bases A9 and G10.1 of the sheared G. A tandem base pair, as shown previously and in detail for the mHHRz. Thus, the much stronger MnII binding in the tsHHRz is attributed to the interaction between the two external loops, which locks in the RNA fold, trapping the MnII in the tightly bound conformation, whereas the absence of long-range loop-loop interactions in the mHHRz leads to more dynamical and open conformations, decreasing MnII binding.},
note = {1355-8382
Letter},
keywords = {Base Sequence Binding Sites Electron Spin Resonance Spectroscopy Framycetin/chemistry/metabolism Kinetics Manganese/*metabolism Nucleic Acid Conformation RNA, Catalytic/*chemistry/*metabolism Research Support, Non-U.S. Gov't, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Electron paramagnetic resonance (EPR) spectroscopy is used to study the binding of MnII ions to a tertiary stabilized hammer-head ribozyme (tsHHRz) and to compare it with the binding to the minimal hammerhead ribozyme (mHHRz). Continuous wave EPR measurements show that the tsHHRz possesses a single high-affinity MnII binding site with a KD of < or =10 nM at an NaCl concentration of 0.1 M. This dissociation constant is at least two orders of magnitude smaller than the KD determined previously for the single high-affinity MnII site in the mHHRz. In addition, whereas the high-affinity MnII is displaced from the mHHRz upon binding of the aminoglycoside antibiotic neomycin B, it is not from the tsHHRz. Despite these pronounced differences in binding, a comparison between the electron spin echo envelope modulation and hyperfine sublevel correlation spectra of the minimal and tertiary stabilized HHRz demonstrates that the structure of both binding sites is very similar. This suggests that the MnII is located in both ribozymes between the bases A9 and G10.1 of the sheared G. A tandem base pair, as shown previously and in detail for the mHHRz. Thus, the much stronger MnII binding in the tsHHRz is attributed to the interaction between the two external loops, which locks in the RNA fold, trapping the MnII in the tightly bound conformation, whereas the absence of long-range loop-loop interactions in the mHHRz leads to more dynamical and open conformations, decreasing MnII binding.
Francois B, Russell R J, Murray J B, Aboul-ela F, Masquida B, Vicens Q, Westhof E
In: Nucleic Acids Res, vol. 33, no. 17, pp. 5677-5690, 2005, ISBN: 16214802, (1362-4962 (Electronic) Journal Article).
Abstract | Links | BibTeX | Tags: 16S/*chemistry Research Support, Adenine/chemistry Aminoglycosides/*chemistry Anti-Bacterial Agents/*chemistry Anticodon/chemistry Base Sequence Binding Sites Codon/chemistry Crystallography, Molecular Oligoribonucleotides/*chemistry Paromomycin/analogs & derivatives/chemistry RNA, Non-U.S. Gov't Ribosomes/chemistry Ribostamycin/chemistry, Ribosomal, Unité ARN, WESTHOF, X-Ray Framycetin/chemistry Gentamicins/chemistry Kanamycin/chemistry *Models
@article{,
title = {Crystal structures of complexes between aminoglycosides and decoding A site oligonucleotides: role of the number of rings and positive charges in the specific binding leading to miscoding},
author = {B Francois and R J Russell and J B Murray and F Aboul-ela and B Masquida and Q Vicens and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16214802},
isbn = {16214802},
year = {2005},
date = {2005-01-01},
journal = {Nucleic Acids Res},
volume = {33},
number = {17},
pages = {5677-5690},
abstract = {The crystal structures of six complexes between aminoglycoside antibiotics (neamine, gentamicin C1A, kanamycin A, ribostamycin, lividomycin A and neomycin B) and oligonucleotides containing the decoding A site of bacterial ribosomes are reported at resolutions between 2.2 and 3.0 A. Although the number of contacts between the RNA and the aminoglycosides varies between 20 and 31, up to eight direct hydrogen bonds between rings I and II of the neamine moiety are conserved in the observed complexes. The puckered sugar ring I is inserted into the A site helix by stacking against G1491 and forms a pseudo base pair with two H-bonds to the Watson-Crick sites of the universally conserved A1408. This central interaction helps to maintain A1492 and A1493 in a bulged-out conformation. All these structures of the minimal A site RNA complexed to various aminoglycosides display crystal packings with intermolecular contacts between the bulging A1492 and A1493 and the shallow/minor groove of Watson-Crick pairs in a neighbouring helix. In one crystal, one empty A site is observed. In two crystals, two aminoglycosides are bound to the same A site with one bound specifically and the other bound in various ways in the deep/major groove at the edge of the A sites.},
note = {1362-4962 (Electronic)
Journal Article},
keywords = {16S/*chemistry Research Support, Adenine/chemistry Aminoglycosides/*chemistry Anti-Bacterial Agents/*chemistry Anticodon/chemistry Base Sequence Binding Sites Codon/chemistry Crystallography, Molecular Oligoribonucleotides/*chemistry Paromomycin/analogs & derivatives/chemistry RNA, Non-U.S. Gov't Ribosomes/chemistry Ribostamycin/chemistry, Ribosomal, Unité ARN, WESTHOF, X-Ray Framycetin/chemistry Gentamicins/chemistry Kanamycin/chemistry *Models},
pubstate = {published},
tppubtype = {article}
}
The crystal structures of six complexes between aminoglycoside antibiotics (neamine, gentamicin C1A, kanamycin A, ribostamycin, lividomycin A and neomycin B) and oligonucleotides containing the decoding A site of bacterial ribosomes are reported at resolutions between 2.2 and 3.0 A. Although the number of contacts between the RNA and the aminoglycosides varies between 20 and 31, up to eight direct hydrogen bonds between rings I and II of the neamine moiety are conserved in the observed complexes. The puckered sugar ring I is inserted into the A site helix by stacking against G1491 and forms a pseudo base pair with two H-bonds to the Watson-Crick sites of the universally conserved A1408. This central interaction helps to maintain A1492 and A1493 in a bulged-out conformation. All these structures of the minimal A site RNA complexed to various aminoglycosides display crystal packings with intermolecular contacts between the bulging A1492 and A1493 and the shallow/minor groove of Watson-Crick pairs in a neighbouring helix. In one crystal, one empty A site is observed. In two crystals, two aminoglycosides are bound to the same A site with one bound specifically and the other bound in various ways in the deep/major groove at the edge of the A sites.
Westhof E, Filipowicz W
From RNAi to epigenomes: how RNA rules the world Journal Article
In: Chembiochem, vol. 6, no. 2, pp. 441-443, 2005, ISBN: 15651038, (1439-4227 (Print) Journal Article).
Links | BibTeX | Tags: Animals Epigenesis, Genetic *Genome MicroRNAs/genetics/metabolism *Rna *RNA Interference RNA, Plant, Unité ARN, WESTHOF
@article{,
title = {From RNAi to epigenomes: how RNA rules the world},
author = {E Westhof and W Filipowicz},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15651038},
isbn = {15651038},
year = {2005},
date = {2005-01-01},
journal = {Chembiochem},
volume = {6},
number = {2},
pages = {441-443},
note = {1439-4227 (Print)
Journal Article},
keywords = {Animals Epigenesis, Genetic *Genome MicroRNAs/genetics/metabolism *Rna *RNA Interference RNA, Plant, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Niimura N, Mizuno H, Helliwell J, Westhof E (Ed.)
Hydrogen- and Hydration-Sensitive Structural Biology Book
Kubapro Co, Ltd, Tokyo, 2005.
BibTeX | Tags: Unité ARN, WESTHOF
@book{,
title = {Hydrogen- and Hydration-Sensitive Structural Biology},
editor = {N Niimura and H Mizuno and J Helliwell and E Westhof},
year = {2005},
date = {2005-01-01},
publisher = {Kubapro Co, Ltd, Tokyo},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {book}
}
Thompson J D, Holbrook S R, Katoh K, Koehl P, Moras D, Westhof E, Poch O
MAO: a Multiple Alignment Ontology for nucleic acid and protein sequences Journal Article
In: Nucleic Acids Res, vol. 33, no. 13, pp. 4164-4171, 2005, ISBN: 16043635, (1362-4962 Journal Article).
Abstract | Links | BibTeX | Tags: Controlled, Databases, DNA/*methods Sequence Analysis, Genetic Humans Interleukin-1/genetics Internet Research Support, Non-U.S. Gov't Sequence Alignment/*methods Sequence Analysis, Protein/*methods Sequence Analysis, RNA/*methods *Software Systems Integration Vocabulary, Unité ARN, WESTHOF
@article{,
title = {MAO: a Multiple Alignment Ontology for nucleic acid and protein sequences},
author = {J D Thompson and S R Holbrook and K Katoh and P Koehl and D Moras and E Westhof and O Poch},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16043635},
isbn = {16043635},
year = {2005},
date = {2005-01-01},
journal = {Nucleic Acids Res},
volume = {33},
number = {13},
pages = {4164-4171},
abstract = {The application of high-throughput techniques such as genomics, proteomics or transcriptomics means that vast amounts of heterogeneous data are now available in the public databases. Bioinformatics is responding to the challenge with new integrated management systems for data collection, validation and analysis. Multiple alignments of genomic and protein sequences provide an ideal environment for the integration of this mass of information. In the context of the sequence family, structural and functional data can be evaluated and propagated from known to unknown sequences. However, effective integration is being hindered by syntactic and semantic differences between the different data resources and the alignment techniques employed. One solution to this problem is the development of an ontology that systematically defines the terms used in a specific domain. Ontologies are used to share data from different resources, to automatically analyse information and to represent domain knowledge for non-experts. Here, we present MAO, a new ontology for multiple alignments of nucleic and protein sequences. MAO is designed to improve interoperation and data sharing between different alignment protocols for the construction of a high quality, reliable multiple alignment in order to facilitate knowledge extraction and the presentation of the most pertinent information to the biologist.},
note = {1362-4962
Journal Article},
keywords = {Controlled, Databases, DNA/*methods Sequence Analysis, Genetic Humans Interleukin-1/genetics Internet Research Support, Non-U.S. Gov't Sequence Alignment/*methods Sequence Analysis, Protein/*methods Sequence Analysis, RNA/*methods *Software Systems Integration Vocabulary, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The application of high-throughput techniques such as genomics, proteomics or transcriptomics means that vast amounts of heterogeneous data are now available in the public databases. Bioinformatics is responding to the challenge with new integrated management systems for data collection, validation and analysis. Multiple alignments of genomic and protein sequences provide an ideal environment for the integration of this mass of information. In the context of the sequence family, structural and functional data can be evaluated and propagated from known to unknown sequences. However, effective integration is being hindered by syntactic and semantic differences between the different data resources and the alignment techniques employed. One solution to this problem is the development of an ontology that systematically defines the terms used in a specific domain. Ontologies are used to share data from different resources, to automatically analyse information and to represent domain knowledge for non-experts. Here, we present MAO, a new ontology for multiple alignments of nucleic and protein sequences. MAO is designed to improve interoperation and data sharing between different alignment protocols for the construction of a high quality, reliable multiple alignment in order to facilitate knowledge extraction and the presentation of the most pertinent information to the biologist.
Masquida B, Westhof E
Modeling the architecture of structural RNAs within a modular and hierarchical framework Book Chapter
In: Hartmann, R K; Bindereif, A; Schon, A; Westhof, E (Ed.): Handbook of RNA Biochemistry, pp. 536-545, WIiley-Vch Verlag, 2005.
Links | BibTeX | Tags: Modeling Architecture Framework Physicochemical forces Amino acids, Unité ARN, WESTHOF
@inbook{,
title = {Modeling the architecture of structural RNAs within a modular and hierarchical framework},
author = {B Masquida and E Westhof},
editor = {R K Hartmann and A Bindereif and A Schon and E Westhof},
url = {http://onlinelibrary.wiley.com/book/10.1002/9783527619504},
year = {2005},
date = {2005-01-01},
booktitle = {Handbook of RNA Biochemistry},
pages = {536-545},
publisher = {WIiley-Vch Verlag},
keywords = {Modeling Architecture Framework Physicochemical forces Amino acids, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {inbook}
}