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2015
Westhof E
Twenty years of RNA crystallography. Journal Article
In: RNA, vol. 21, no. 4, pp. 486-487, 2015, ISBN: 25780106.
Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Twenty years of RNA crystallography.},
author = {E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25780106?dopt=Abstract},
doi = {10.1261/rna.049726.115},
isbn = {25780106},
year = {2015},
date = {2015-01-01},
journal = {RNA},
volume = {21},
number = {4},
pages = {486-487},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Rozov A, Demeshkina N, Westhof E, Yusupov M, Yusupova G
Structural insights into the translational infidelity mechanism. Journal Article
In: Nat Commun, vol. 6, pp. 7251, 2015, ISBN: 26037619.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Structural insights into the translational infidelity mechanism.},
author = {A Rozov and N Demeshkina and E Westhof and M Yusupov and G Yusupova},
url = {http://www.ncbi.nlm.nih.gov/pubmed/26037619?dopt=Abstract},
doi = {10.1038/ncomms8251},
isbn = {26037619},
year = {2015},
date = {2015-01-01},
journal = {Nat Commun},
volume = {6},
pages = {7251},
abstract = {The decoding of mRNA on the ribosome is the least accurate process during genetic information transfer. Here we propose a unified decoding mechanism based on 11 high-resolution X-ray structures of the 70S ribosome that explains the occurrence of missense errors during translation. We determined ribosome structures in rare states where incorrect tRNAs were incorporated into the peptidyl-tRNA-binding site. These structures show that in the codon-anticodon duplex, a G·U mismatch adopts the Watson-Crick geometry, indicating a shift in the tautomeric equilibrium or ionization of the nucleobase. Additional structures with mismatches in the 70S decoding centre show that the binding of any tRNA induces identical rearrangements in the centre, which favours either isosteric or close to the Watson-Crick geometry codon-anticodon pairs. Overall, the results suggest that a mismatch escapes discrimination by preserving the shape of a Watson-Crick pair and indicate that geometric selection via tautomerism or ionization dominates the translational infidelity mechanism.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The decoding of mRNA on the ribosome is the least accurate process during genetic information transfer. Here we propose a unified decoding mechanism based on 11 high-resolution X-ray structures of the 70S ribosome that explains the occurrence of missense errors during translation. We determined ribosome structures in rare states where incorrect tRNAs were incorporated into the peptidyl-tRNA-binding site. These structures show that in the codon-anticodon duplex, a G·U mismatch adopts the Watson-Crick geometry, indicating a shift in the tautomeric equilibrium or ionization of the nucleobase. Additional structures with mismatches in the 70S decoding centre show that the binding of any tRNA induces identical rearrangements in the centre, which favours either isosteric or close to the Watson-Crick geometry codon-anticodon pairs. Overall, the results suggest that a mismatch escapes discrimination by preserving the shape of a Watson-Crick pair and indicate that geometric selection via tautomerism or ionization dominates the translational infidelity mechanism.
Miao Z, Westhof E
A Large-Scale Assessment of Nucleic Acids Binding Site Prediction Programs. Journal Article
In: PLoS Comput Biol, vol. 11, no. 12, pp. e1004639, 2015, ISBN: 26681179.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {A Large-Scale Assessment of Nucleic Acids Binding Site Prediction Programs.},
author = {Z Miao and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/26681179?dopt=Abstract},
doi = {10.1371/journal.pcbi.1004639},
isbn = {26681179},
year = {2015},
date = {2015-01-01},
journal = {PLoS Comput Biol},
volume = {11},
number = {12},
pages = {e1004639},
abstract = {Computational prediction of nucleic acid binding sites in proteins are necessary to disentangle functional mechanisms in most biological processes and to explore the binding mechanisms. Several strategies have been proposed, but the state-of-the-art approaches display a great diversity in i) the definition of nucleic acid binding sites; ii) the training and test datasets; iii) the algorithmic methods for the prediction strategies; iv) the performance measures and v) the distribution and availability of the prediction programs. Here we report a large-scale assessment of 19 web servers and 3 stand-alone programs on 41 datasets including more than 5000 proteins derived from 3D structures of protein-nucleic acid complexes. Well-defined binary assessment criteria (specificity, sensitivity, precision, accuracy…) are applied. We found that i) the tools have been greatly improved over the years; ii) some of the approaches suffer from theoretical defects and there is still room for sorting out the essential mechanisms of binding; iii) RNA binding and DNA binding appear to follow similar driving forces and iv) dataset bias may exist in some methods.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Computational prediction of nucleic acid binding sites in proteins are necessary to disentangle functional mechanisms in most biological processes and to explore the binding mechanisms. Several strategies have been proposed, but the state-of-the-art approaches display a great diversity in i) the definition of nucleic acid binding sites; ii) the training and test datasets; iii) the algorithmic methods for the prediction strategies; iv) the performance measures and v) the distribution and availability of the prediction programs. Here we report a large-scale assessment of 19 web servers and 3 stand-alone programs on 41 datasets including more than 5000 proteins derived from 3D structures of protein-nucleic acid complexes. Well-defined binary assessment criteria (specificity, sensitivity, precision, accuracy…) are applied. We found that i) the tools have been greatly improved over the years; ii) some of the approaches suffer from theoretical defects and there is still room for sorting out the essential mechanisms of binding; iii) RNA binding and DNA binding appear to follow similar driving forces and iv) dataset bias may exist in some methods.
Miao Z, Westhof E
Prediction of nucleic acid binding probability in proteins: a neighboring residue network based score. Journal Article
In: Nucleic Acids Res, vol. 43, no. 11, pp. 5340-5351, 2015, ISBN: 25940624.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Prediction of nucleic acid binding probability in proteins: a neighboring residue network based score.},
author = {Z Miao and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25940624?dopt=Abstract},
doi = {10.1093/nar/gkv446},
isbn = {25940624},
year = {2015},
date = {2015-01-01},
journal = {Nucleic Acids Res},
volume = {43},
number = {11},
pages = {5340-5351},
abstract = {We describe a general binding score for predicting the nucleic acid binding probability in proteins. The score is directly derived from physicochemical and evolutionary features and integrates a residue neighboring network approach. Our process achieves stable and high accuracies on both DNA- and RNA-binding proteins and illustrates how the main driving forces for nucleic acid binding are common. Because of the effective integration of the synergetic effects of the network of neighboring residues and the fact that the prediction yields a hierarchical scoring on the protein surface, energy funnels for nucleic acid binding appear on protein surfaces, pointing to the dynamic process occurring in the binding of nucleic acids to proteins.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
We describe a general binding score for predicting the nucleic acid binding probability in proteins. The score is directly derived from physicochemical and evolutionary features and integrates a residue neighboring network approach. Our process achieves stable and high accuracies on both DNA- and RNA-binding proteins and illustrates how the main driving forces for nucleic acid binding are common. Because of the effective integration of the synergetic effects of the network of neighboring residues and the fact that the prediction yields a hierarchical scoring on the protein surface, energy funnels for nucleic acid binding appear on protein surfaces, pointing to the dynamic process occurring in the binding of nucleic acids to proteins.
D'Ascenzo L, Auffinger P
106 Ion-π interactions in biomolecular systems. Journal Article
In: J Biomol Struct Dyn, vol. 33, no. Suppl 1, pp. 67, 2015, ISBN: 26103317.
Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {106 Ion-π interactions in biomolecular systems.},
author = {L D'Ascenzo and P Auffinger},
url = {http://www.ncbi.nlm.nih.gov/pubmed/26103317?dopt=Abstract},
doi = {10.1080/07391102.2015.1032668.},
isbn = {26103317},
year = {2015},
date = {2015-01-01},
journal = {J Biomol Struct Dyn},
volume = {33},
number = {Suppl 1},
pages = {67},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Ryckelynck M, Baudrey S, Rick C, Marin A, Coldren F, Westhof E, Griffiths A D
Using droplet-based microfluidics to improve the catalytic properties of RNA under multiple-turnover conditions. Journal Article
In: RNA, vol. 21, no. 3, pp. 458-469, 2015, ISBN: 25605963.
Abstract | Links | BibTeX | Tags: RNA droplet-based microfluidics high-throughput screening in vitro evolution ribozymes, RYCKELYNCK, Unité ARN, WESTHOF
@article{,
title = {Using droplet-based microfluidics to improve the catalytic properties of RNA under multiple-turnover conditions.},
author = {M Ryckelynck and S Baudrey and C Rick and A Marin and F Coldren and E Westhof and A D Griffiths},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25605963?dopt=Abstract},
doi = {10.1261/rna.048033.114},
isbn = {25605963},
year = {2015},
date = {2015-01-01},
journal = {RNA},
volume = {21},
number = {3},
pages = {458-469},
abstract = {In vitro evolution methodologies are powerful approaches to identify RNA with new functionalities. While Systematic Evolution of Ligands by Exponential enrichment (SELEX) is an efficient approach to generate new RNA aptamers, it is less suited for the isolation of efficient ribozymes as it does not select directly for the catalysis. In vitro compartmentalization (IVC) in aqueous droplets in emulsions allows catalytic RNAs to be selected under multiple-turnover conditions but suffers severe limitations that can be overcome using the droplet-based microfluidics workflow described in this paper. Using microfluidics, millions of genes in a library can be individually compartmentalized in highly monodisperse aqueous droplets and serial operations performed on them. This allows the different steps of the evolution process (gene amplification, transcription, and phenotypic assay) to be uncoupled, making the method highly flexible, applicable to the selection and evolution of a variety of RNAs, and easily adaptable for evolution of DNA or proteins. To demonstrate the method, we performed cycles of random mutagenesis and selection to evolve the X-motif, a ribozyme which, like many ribozymes selected using SELEX, has limited multiple-turnover activity. This led to the selection of variants, likely to be the optimal ribozymes that can be generated using point mutagenesis alone, with a turnover number under multiple-turnover conditions, kss cat, ∼28-fold higher than the original X-motif, primarily due to an increase in the rate of product release, the rate-limiting step in the multiple-turnover reaction.},
keywords = {RNA droplet-based microfluidics high-throughput screening in vitro evolution ribozymes, RYCKELYNCK, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
In vitro evolution methodologies are powerful approaches to identify RNA with new functionalities. While Systematic Evolution of Ligands by Exponential enrichment (SELEX) is an efficient approach to generate new RNA aptamers, it is less suited for the isolation of efficient ribozymes as it does not select directly for the catalysis. In vitro compartmentalization (IVC) in aqueous droplets in emulsions allows catalytic RNAs to be selected under multiple-turnover conditions but suffers severe limitations that can be overcome using the droplet-based microfluidics workflow described in this paper. Using microfluidics, millions of genes in a library can be individually compartmentalized in highly monodisperse aqueous droplets and serial operations performed on them. This allows the different steps of the evolution process (gene amplification, transcription, and phenotypic assay) to be uncoupled, making the method highly flexible, applicable to the selection and evolution of a variety of RNAs, and easily adaptable for evolution of DNA or proteins. To demonstrate the method, we performed cycles of random mutagenesis and selection to evolve the X-motif, a ribozyme which, like many ribozymes selected using SELEX, has limited multiple-turnover activity. This led to the selection of variants, likely to be the optimal ribozymes that can be generated using point mutagenesis alone, with a turnover number under multiple-turnover conditions, kss cat, ∼28-fold higher than the original X-motif, primarily due to an increase in the rate of product release, the rate-limiting step in the multiple-turnover reaction.
Miao Z, Adamiak R W, Blanchet M F, Boniecki M, Bujnicki J M, Chen S J, Cheng C, Chojnowski G, Chou F C, Cordero P, Cruz J A, Ferré-D'amaré A R, Das R, Ding F, Dokholyan N V, Dunin-Horkawicz S, Kladwang W, Krokhotin A, Lach G, Magnus M, Major F, Mann T H, Masquida B, Matelska D, Meyer M, Peselis A, Popenda M, Purzycka K J, Serganov A, Stasiewicz J, Szachniuk M, Tandon A, Tian S, Wang J, Xiao Y, Xu X, Zhang J, Zhao P, Zok T, Westhof E
RNA-Puzzles Round II: assessment of RNA structure prediction programs applied to three large RNA structures. Journal Article
In: RNA, vol. 21, no. 6, pp. 1066-1084, 2015, ISBN: 25883046.
Abstract | Links | BibTeX | Tags: 3D prediction X-ray structures bioinformatics force fields models structure quality, Unité ARN, WESTHOF
@article{,
title = {RNA-Puzzles Round II: assessment of RNA structure prediction programs applied to three large RNA structures.},
author = {Z Miao and R W Adamiak and M F Blanchet and M Boniecki and J M Bujnicki and S J Chen and C Cheng and G Chojnowski and F C Chou and P Cordero and J A Cruz and A R Ferré-D'amaré and R Das and F Ding and N V Dokholyan and S Dunin-Horkawicz and W Kladwang and A Krokhotin and G Lach and M Magnus and F Major and T H Mann and B Masquida and D Matelska and M Meyer and A Peselis and M Popenda and K J Purzycka and A Serganov and J Stasiewicz and M Szachniuk and A Tandon and S Tian and J Wang and Y Xiao and X Xu and J Zhang and P Zhao and T Zok and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25883046},
doi = {10.1261/rna.049502.114},
isbn = {25883046},
year = {2015},
date = {2015-01-01},
journal = {RNA},
volume = {21},
number = {6},
pages = {1066-1084},
abstract = {This paper is a report of a second round of RNA-Puzzles, a collective and blind experiment in three-dimensional (3D) RNA structure prediction. Three puzzles, Puzzles 5, 6, and 10, represented sequences of three large RNA structures with limited or no homology with previously solved RNA molecules. A lariat-capping ribozyme, as well as riboswitches complexed to adenosylcobalamin and tRNA, were predicted by seven groups using RNAComposer, ModeRNA/SimRNA, Vfold, Rosetta, DMD, MC-Fold, 3dRNA, and AMBER refinement. Some groups derived models using data from state-of-the-art chemical-mapping methods (SHAPE, DMS, CMCT, and mutate-and-map). The comparisons between the predictions and the three subsequently released crystallographic structures, solved at diffraction resolutions of 2.5-3.2 Å, were carried out automatically using various sets of quality indicators. The comparisons clearly demonstrate the state of present-day de novo prediction abilities as well as the limitations of these state-of-the-art methods. All of the best prediction models have similar topologies to the native structures, which suggests that computational methods for RNA structure prediction can already provide useful structural information for biological problems. However, the prediction accuracy for non-Watson-Crick interactions, key to proper folding of RNAs, is low and some predicted models had high Clash Scores. These two difficulties point to some of the continuing bottlenecks in RNA structure prediction. All submitted models are available for download at http://ahsoka.u-strasbg.fr/rnapuzzles/.},
keywords = {3D prediction X-ray structures bioinformatics force fields models structure quality, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
This paper is a report of a second round of RNA-Puzzles, a collective and blind experiment in three-dimensional (3D) RNA structure prediction. Three puzzles, Puzzles 5, 6, and 10, represented sequences of three large RNA structures with limited or no homology with previously solved RNA molecules. A lariat-capping ribozyme, as well as riboswitches complexed to adenosylcobalamin and tRNA, were predicted by seven groups using RNAComposer, ModeRNA/SimRNA, Vfold, Rosetta, DMD, MC-Fold, 3dRNA, and AMBER refinement. Some groups derived models using data from state-of-the-art chemical-mapping methods (SHAPE, DMS, CMCT, and mutate-and-map). The comparisons between the predictions and the three subsequently released crystallographic structures, solved at diffraction resolutions of 2.5-3.2 Å, were carried out automatically using various sets of quality indicators. The comparisons clearly demonstrate the state of present-day de novo prediction abilities as well as the limitations of these state-of-the-art methods. All of the best prediction models have similar topologies to the native structures, which suggests that computational methods for RNA structure prediction can already provide useful structural information for biological problems. However, the prediction accuracy for non-Watson-Crick interactions, key to proper folding of RNAs, is low and some predicted models had high Clash Scores. These two difficulties point to some of the continuing bottlenecks in RNA structure prediction. All submitted models are available for download at http://ahsoka.u-strasbg.fr/rnapuzzles/.
D'Ascenzo L, Auffinger P
In: Acta Crystallogr B Struct Sci Cryst Eng Mater, vol. 71, no. Pt 2, pp. 164-175, 2015, ISBN: 25827369.
Abstract | Links | BibTeX | Tags: biomolecular systems crystal engineering pharmaceuticals supramolecular motifs, Unité ARN, WESTHOF
@article{,
title = {A comprehensive classification and nomenclature of carboxyl-carboxyl(ate) supramolecular motifs and related catemers: implications for biomolecular systems.},
author = {L D'Ascenzo and P Auffinger},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25827369?dopt=Abstract},
doi = {10.1107/S205252061500270X},
isbn = {25827369},
year = {2015},
date = {2015-01-01},
journal = {Acta Crystallogr B Struct Sci Cryst Eng Mater},
volume = {71},
number = {Pt 2},
pages = {164-175},
abstract = {Carboxyl and carboxylate groups form important supramolecular motifs (synthons). Besides carboxyl cyclic dimers, carboxyl and carboxylate groups can associate through a single hydrogen bond. Carboxylic groups can further form polymeric-like catemer chains within crystals. To date, no exhaustive classification of these motifs has been established. In this work, 17 association types were identified (13 carboxyl-carboxyl and 4 carboxyl-carboxylate motifs) by taking into account the syn and anti carboxyl conformers, as well as the syn and anti lone pairs of the O atoms. From these data, a simple rule was derived stating that only eight distinct catemer motifs involving repetitive combinations of syn and anti carboxyl groups can be formed. Examples extracted from the Cambridge Structural Database (CSD) for all identified dimers and catemers are presented, as well as statistical data related to their occurrence and conformational preferences. The inter-carboxyl(ate) and carboxyl(ate)-water hydrogen-bond properties are described, stressing the occurrence of very short (strong) hydrogen bonds. The precise characterization and classification of these supramolecular motifs should be of interest in crystal engineering, pharmaceutical and also biomolecular sciences, where similar motifs occur in the form of pairs of Asp/Glu amino acids or motifs involving ligands bearing carboxyl(ate) groups. Hence, we present data emphasizing how the analysis of hydrogen-containing small molecules of high resolution can help understand structural aspects of larger and more complex biomolecular systems of lower resolution.},
keywords = {biomolecular systems crystal engineering pharmaceuticals supramolecular motifs, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Carboxyl and carboxylate groups form important supramolecular motifs (synthons). Besides carboxyl cyclic dimers, carboxyl and carboxylate groups can associate through a single hydrogen bond. Carboxylic groups can further form polymeric-like catemer chains within crystals. To date, no exhaustive classification of these motifs has been established. In this work, 17 association types were identified (13 carboxyl-carboxyl and 4 carboxyl-carboxylate motifs) by taking into account the syn and anti carboxyl conformers, as well as the syn and anti lone pairs of the O atoms. From these data, a simple rule was derived stating that only eight distinct catemer motifs involving repetitive combinations of syn and anti carboxyl groups can be formed. Examples extracted from the Cambridge Structural Database (CSD) for all identified dimers and catemers are presented, as well as statistical data related to their occurrence and conformational preferences. The inter-carboxyl(ate) and carboxyl(ate)-water hydrogen-bond properties are described, stressing the occurrence of very short (strong) hydrogen bonds. The precise characterization and classification of these supramolecular motifs should be of interest in crystal engineering, pharmaceutical and also biomolecular sciences, where similar motifs occur in the form of pairs of Asp/Glu amino acids or motifs involving ligands bearing carboxyl(ate) groups. Hence, we present data emphasizing how the analysis of hydrogen-containing small molecules of high resolution can help understand structural aspects of larger and more complex biomolecular systems of lower resolution.
2014
Westhof E, Yusupov M, Yusupova G
Recognition of Watson-Crick base pairs: constraints and limits due to geometric selection and tautomerism Journal Article
In: F1000Prime Rep, vol. 6, pp. 19, 2014, ISBN: 24765524.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Recognition of Watson-Crick base pairs: constraints and limits due to geometric selection and tautomerism},
author = {E Westhof and M Yusupov and G Yusupova},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24765524},
doi = {10.12703/P6-19},
isbn = {24765524},
year = {2014},
date = {2014-01-01},
journal = {F1000Prime Rep},
volume = {6},
pages = {19},
abstract = {The natural bases of nucleic acids have a strong preference for one tautomer form, guaranteeing fidelity in their hydrogen bonding potential. However, base pairs observed in recent crystal structures of polymerases and ribosomes are best explained by an alternative base tautomer, leading to the formation of base pairs with Watson-Crick-like geometries. These observations set limits to geometric selection in molecular recognition of complementary Watson-Crick pairs for fidelity in replication and translation processes.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The natural bases of nucleic acids have a strong preference for one tautomer form, guaranteeing fidelity in their hydrogen bonding potential. However, base pairs observed in recent crystal structures of polymerases and ribosomes are best explained by an alternative base tautomer, leading to the formation of base pairs with Watson-Crick-like geometries. These observations set limits to geometric selection in molecular recognition of complementary Watson-Crick pairs for fidelity in replication and translation processes.
Westhof E
Isostericity and tautomerism of base pairs in nucleic acids. Journal Article
In: FEBS Lett, vol. 588, no. 15, pp. 2464-2469, 2014, ISBN: 24950426.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Isostericity and tautomerism of base pairs in nucleic acids.},
author = {E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24950426?dopt=Abstract},
doi = {10.1016/j.febslet.2014.06.031.},
isbn = {24950426},
year = {2014},
date = {2014-01-01},
journal = {FEBS Lett},
volume = {588},
number = {15},
pages = {2464-2469},
abstract = {The natural bases of nucleic acids form a great variety of base pairs with at least two hydrogen bonds between them. They are classified in twelve main families, with the Watson-Crick family being one of them. In a given family, some of the base pairs are isosteric between them, meaning that the positions and the distances between the C1' carbon atoms are very similar. The isostericity of Watson-Crick pairs between the complementary bases forms the basis of RNA helices and of the resulting RNA secondary structure. Several defined suites of non-Watson-Crick base pairs assemble into RNA modules that form recurrent, rather regular, building blocks of the tertiary architecture of folded RNAs. RNA modules are intrinsic to RNA architecture are therefore disconnected from a biological function specifically attached to a RNA sequence. RNA modules occur in all kingdoms of life and in structured RNAs with diverse functions. Because of chemical and geometrical constraints, isostericity between non-Watson-Crick pairs is restricted and this leads to higher sequence conservation in RNA modules with, consequently, greater difficulties in extracting 3D information from sequence analysis. Nucleic acid helices have to be recognised in several biological processes like replication or translational decoding. In polymerases and the ribosomal decoding site, the recognition occurs on the minor groove sides of the helical fragments. With the use of alternative conformations, protonated or tautomeric forms of the bases, some base pairs with Watson-Crick-like geometries can form and be stabilized. Several of these pairs with Watson-Crick-like geometries extend the concept of isostericity beyond the number of isosteric pairs formed between complementary bases. These observations set therefore limits and constraints to geometric selection in molecular recognition of complementary Watson-Crick pairs for fidelity in replication and translation processes.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The natural bases of nucleic acids form a great variety of base pairs with at least two hydrogen bonds between them. They are classified in twelve main families, with the Watson-Crick family being one of them. In a given family, some of the base pairs are isosteric between them, meaning that the positions and the distances between the C1' carbon atoms are very similar. The isostericity of Watson-Crick pairs between the complementary bases forms the basis of RNA helices and of the resulting RNA secondary structure. Several defined suites of non-Watson-Crick base pairs assemble into RNA modules that form recurrent, rather regular, building blocks of the tertiary architecture of folded RNAs. RNA modules are intrinsic to RNA architecture are therefore disconnected from a biological function specifically attached to a RNA sequence. RNA modules occur in all kingdoms of life and in structured RNAs with diverse functions. Because of chemical and geometrical constraints, isostericity between non-Watson-Crick pairs is restricted and this leads to higher sequence conservation in RNA modules with, consequently, greater difficulties in extracting 3D information from sequence analysis. Nucleic acid helices have to be recognised in several biological processes like replication or translational decoding. In polymerases and the ribosomal decoding site, the recognition occurs on the minor groove sides of the helical fragments. With the use of alternative conformations, protonated or tautomeric forms of the bases, some base pairs with Watson-Crick-like geometries can form and be stabilized. Several of these pairs with Watson-Crick-like geometries extend the concept of isostericity beyond the number of isosteric pairs formed between complementary bases. These observations set therefore limits and constraints to geometric selection in molecular recognition of complementary Watson-Crick pairs for fidelity in replication and translation processes.
Ren A, Košutić M, Rajashankar K R, Frener M, Santner T, Westhof E, Micura R, Patel D J
In-line alignment and Mg(2+) coordination at the cleavage site of the env22 twister ribozyme. Journal Article
In: Nat Commun, vol. 5, pp. 5534, 2014, ISBN: 25410397.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {In-line alignment and Mg(2+) coordination at the cleavage site of the env22 twister ribozyme.},
author = {A Ren and M Košutić and K R Rajashankar and M Frener and T Santner and E Westhof and R Micura and D J Patel},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25410397?dopt=Abstract},
doi = {10.1038/ncomms6534},
isbn = {25410397},
year = {2014},
date = {2014-01-01},
journal = {Nat Commun},
volume = {5},
pages = {5534},
abstract = {Small self-cleaving nucleolytic ribozymes contain catalytic domains that accelerate site-specific cleavage/ligation of phosphodiester backbones. We report on the 2.9-Å crystal structure of the env22 twister ribozyme, which adopts a compact tertiary fold stabilized by co-helical stacking, double-pseudoknot formation and long-range pairing interactions. The U-A cleavage site adopts a splayed-apart conformation with the modelled 2'-O of U positioned for in-line attack on the adjacent to-be-cleaved P-O5' bond. Both an invariant guanosine and a Mg(2+) are directly coordinated to the non-bridging phosphate oxygens at the U-A cleavage step, with the former positioned to contribute to catalysis and the latter to structural integrity. The impact of key mutations on cleavage activity identified an invariant guanosine that contributes to catalysis. Our structure of the in-line aligned env22 twister ribozyme is compared with two recently reported twister ribozymes structures, which adopt similar global folds, but differ in conformational features around the cleavage site.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Small self-cleaving nucleolytic ribozymes contain catalytic domains that accelerate site-specific cleavage/ligation of phosphodiester backbones. We report on the 2.9-Å crystal structure of the env22 twister ribozyme, which adopts a compact tertiary fold stabilized by co-helical stacking, double-pseudoknot formation and long-range pairing interactions. The U-A cleavage site adopts a splayed-apart conformation with the modelled 2'-O of U positioned for in-line attack on the adjacent to-be-cleaved P-O5' bond. Both an invariant guanosine and a Mg(2+) are directly coordinated to the non-bridging phosphate oxygens at the U-A cleavage step, with the former positioned to contribute to catalysis and the latter to structural integrity. The impact of key mutations on cleavage activity identified an invariant guanosine that contributes to catalysis. Our structure of the in-line aligned env22 twister ribozyme is compared with two recently reported twister ribozymes structures, which adopt similar global folds, but differ in conformational features around the cleavage site.
Hartmann R K, Bindereif A, Schon A, Westhof E (Ed.)
Handbook of RNA Biochemistry Book
OUVRAGE, Wiley-Vch-Verlag, 2014.
BibTeX | Tags: Unité ARN, WESTHOF
@book{,
title = {Handbook of RNA Biochemistry},
editor = {R K Hartmann and A Bindereif and A Schon and E Westhof},
year = {2014},
date = {2014-01-01},
volume = {1},
publisher = {Wiley-Vch-Verlag},
edition = {OUVRAGE},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {book}
}
Vicens Q, Westhof E
Biogenesis of Circular RNAs. Journal Article
In: Cell, vol. 159, no. 1, pp. 13-14, 2014, ISBN: 25259915.
Abstract | Links | BibTeX | Tags: ERIANI, Unité ARN, WESTHOF
@article{,
title = {Biogenesis of Circular RNAs.},
author = {Q Vicens and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25259915?dopt=Abstract},
doi = {10.1016/j.cell.2014.09.005},
isbn = {25259915},
year = {2014},
date = {2014-01-01},
journal = {Cell},
volume = {159},
number = {1},
pages = {13-14},
abstract = {Circular RNAs are generated during splicing through various mechanisms. Ashwal-Fluss et al. demonstrate that exon circularization and linear splicing compete with each other in a tissue-specific fashion, and Zhang et al. show that exon circularization depends on flanking intronic complementary sequences. Both papers show that several types of circular RNA transcripts can be produced from a single gene.},
keywords = {ERIANI, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Circular RNAs are generated during splicing through various mechanisms. Ashwal-Fluss et al. demonstrate that exon circularization and linear splicing compete with each other in a tissue-specific fashion, and Zhang et al. show that exon circularization depends on flanking intronic complementary sequences. Both papers show that several types of circular RNA transcripts can be produced from a single gene.
Sesto N, Touchon M, Andrade J M, Kondo J, Rocha E P, Arraiano C M, Archambaud C, Westhof E, Romby P, Cossart P
A PNPase Dependent CRISPR System in Listeria. Journal Article
In: PLoS Genet, vol. 10, no. 1, pp. e1004065, 2014, ISBN: 24415952.
Abstract | Links | BibTeX | Tags: ROMBY, Unité ARN, WESTHOF
@article{,
title = {A PNPase Dependent CRISPR System in Listeria.},
author = {N Sesto and M Touchon and J M Andrade and J Kondo and E P Rocha and C M Arraiano and C Archambaud and E Westhof and P Romby and P Cossart},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24415952?dopt=Abstract},
doi = {10.1371/journal.pgen.1004065},
isbn = {24415952},
year = {2014},
date = {2014-01-01},
journal = {PLoS Genet},
volume = {10},
number = {1},
pages = {e1004065},
abstract = {The human bacterial pathogen Listeria monocytogenes is emerging as a model organism to study RNA-mediated regulation in pathogenic bacteria. A class of non-coding RNAs called CRISPRs (clustered regularly interspaced short palindromic repeats) has been described to confer bacterial resistance against invading bacteriophages and conjugative plasmids. CRISPR function relies on the activity of CRISPR associated (cas) genes that encode a large family of proteins with nuclease or helicase activities and DNA and RNA binding domains. Here, we characterized a CRISPR element (RliB) that is expressed and processed in the L. monocytogenes strain EGD-e, which is completely devoid of cas genes. Structural probing revealed that RliB has an unexpected secondary structure comprising basepair interactions between the repeats and the adjacent spacers in place of canonical hairpins formed by the palindromic repeats. Moreover, in contrast to other CRISPR-Cas systems identified in Listeria, RliB-CRISPR is ubiquitously present among Listeria genomes at the same genomic locus and is never associated with the cas genes. We showed that RliB-CRISPR is a substrate for the endogenously encoded polynucleotide phosphorylase (PNPase) enzyme. The spacers of the different Listeria RliB-CRISPRs share many sequences with temperate and virulent phages. Furthermore, we show that a cas-less RliB-CRISPR lowers the acquisition frequency of a plasmid carrying the matching protospacer, provided that trans encoded cas genes of a second CRISPR-Cas system are present in the genome. Importantly, we show that PNPase is required for RliB-CRISPR mediated DNA interference. Altogether, our data reveal a yet undescribed CRISPR system whose both processing and activity depend on PNPase, highlighting a new and unexpected function for PNPase in "CRISPRology".},
keywords = {ROMBY, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The human bacterial pathogen Listeria monocytogenes is emerging as a model organism to study RNA-mediated regulation in pathogenic bacteria. A class of non-coding RNAs called CRISPRs (clustered regularly interspaced short palindromic repeats) has been described to confer bacterial resistance against invading bacteriophages and conjugative plasmids. CRISPR function relies on the activity of CRISPR associated (cas) genes that encode a large family of proteins with nuclease or helicase activities and DNA and RNA binding domains. Here, we characterized a CRISPR element (RliB) that is expressed and processed in the L. monocytogenes strain EGD-e, which is completely devoid of cas genes. Structural probing revealed that RliB has an unexpected secondary structure comprising basepair interactions between the repeats and the adjacent spacers in place of canonical hairpins formed by the palindromic repeats. Moreover, in contrast to other CRISPR-Cas systems identified in Listeria, RliB-CRISPR is ubiquitously present among Listeria genomes at the same genomic locus and is never associated with the cas genes. We showed that RliB-CRISPR is a substrate for the endogenously encoded polynucleotide phosphorylase (PNPase) enzyme. The spacers of the different Listeria RliB-CRISPRs share many sequences with temperate and virulent phages. Furthermore, we show that a cas-less RliB-CRISPR lowers the acquisition frequency of a plasmid carrying the matching protospacer, provided that trans encoded cas genes of a second CRISPR-Cas system are present in the genome. Importantly, we show that PNPase is required for RliB-CRISPR mediated DNA interference. Altogether, our data reveal a yet undescribed CRISPR system whose both processing and activity depend on PNPase, highlighting a new and unexpected function for PNPase in "CRISPRology".
Meyer M, Nielsen H, Oliéric V, Roblin P, Johansen S D, Westhof E, Masquida B
Speciation of a group I intron into a lariat capping ribozyme. Journal Article
In: Proc Natl Acad Sci U S A, vol. 111, no. 21, pp. 7659-7664, 2014, ISBN: 24821772.
Abstract | Links | BibTeX | Tags: GIR1 RNA catalysis RNA structure SAXS crystallography, Unité ARN, WESTHOF
@article{,
title = {Speciation of a group I intron into a lariat capping ribozyme.},
author = {M Meyer and H Nielsen and V Oliéric and P Roblin and S D Johansen and E Westhof and B Masquida},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24821772?dopt=Abstract},
doi = {10.1073/pnas.1322248111},
isbn = {24821772},
year = {2014},
date = {2014-01-01},
journal = {Proc Natl Acad Sci U S A},
volume = {111},
number = {21},
pages = {7659-7664},
abstract = {The lariat-capping (LC) ribozyme is a natural ribozyme isolated from eukaryotic microorganisms. Despite apparent structural similarity to group I introns, the LC ribozyme catalyzes cleavage by a 2',5' branching reaction, leaving the 3' product with a 3-nt lariat cap that functionally substitutes for a conventional mRNA cap in the downstream pre-mRNA encoding a homing endonuclease. We describe the crystal structures of the precleavage and postcleavage LC ribozymes, which suggest that structural features inherited from group I ribozymes have undergone speciation due to profound changes in molecular selection pressure, ultimately giving rise to an original branching ribozyme family. The structures elucidate the role of key elements that regulate the activity of the LC ribozyme by conformational switching and suggest a mechanism by which the signal for branching is transmitted to the catalytic core. The structures also show how conserved interactions twist residues, forming the lariat to join chemical groups involved in branching.},
keywords = {GIR1 RNA catalysis RNA structure SAXS crystallography, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The lariat-capping (LC) ribozyme is a natural ribozyme isolated from eukaryotic microorganisms. Despite apparent structural similarity to group I introns, the LC ribozyme catalyzes cleavage by a 2',5' branching reaction, leaving the 3' product with a 3-nt lariat cap that functionally substitutes for a conventional mRNA cap in the downstream pre-mRNA encoding a homing endonuclease. We describe the crystal structures of the precleavage and postcleavage LC ribozymes, which suggest that structural features inherited from group I ribozymes have undergone speciation due to profound changes in molecular selection pressure, ultimately giving rise to an original branching ribozyme family. The structures elucidate the role of key elements that regulate the activity of the LC ribozyme by conformational switching and suggest a mechanism by which the signal for branching is transmitted to the catalytic core. The structures also show how conserved interactions twist residues, forming the lariat to join chemical groups involved in branching.
2012
Westhof E
RNA modeling, naturally. Journal Article
In: Proc Natl Acad Sci U S A, vol. 109, no. 8, pp. 2691-2692, 2012, ISBN: 22308479, (Published online: February 3, 2012).
Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {RNA modeling, naturally.},
author = {E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22308479},
doi = {10.1073/pnas.1121363109},
isbn = {22308479},
year = {2012},
date = {2012-01-01},
journal = {Proc Natl Acad Sci U S A},
volume = {109},
number = {8},
pages = {2691-2692},
note = {Published online: February 3, 2012},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Salian S, Matt T, Akbergenov R, Harish S, Meyer M, Duscha S, Shcherbakov D, Bernet B B, Vasella A, Westhof E, Bottger E C
Structure-activity relationships among the kanamycin aminoglycosides: role of ring I hydroxy and amino groups. Journal Article
In: Antimicrob Agents Chemother, vol. 56, no. 12, pp. 6104-6108, 2012, ISBN: 22948879.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Structure-activity relationships among the kanamycin aminoglycosides: role of ring I hydroxy and amino groups.},
author = {S Salian and T Matt and R Akbergenov and S Harish and M Meyer and S Duscha and D Shcherbakov and B B Bernet and A Vasella and E Westhof and E C Bottger},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22948879?dopt=Abstract},
doi = {10.1128/AAC.01326-12},
isbn = {22948879},
year = {2012},
date = {2012-01-01},
journal = {Antimicrob Agents Chemother},
volume = {56},
number = {12},
pages = {6104-6108},
abstract = {The kanamycins form an important subgroup of the 4,6-disubstituted 2-deoxystreptamine aminoglycoside antibiotics, comprising kanamycin A, kanamycin B, tobramycin and dibekacin. These compounds interfere with protein synthesis by targeting the ribosomal decoding A site and they differ in the number and location of amino and hydroxy groups of the glucopyranosyl moiety (ring I). We have synthesized kanamycin analogues characterized by subtle variations of the 2' and 6' substituents of ring I. The functional activities of the kanamycins and the synthesized analogues were investigated i) in cell-free translation assays on wild-type and mutant bacterial ribosomes to study drug-target interaction, ii) in MIC assays to assess antibacterial activity, and iii) in rabbit reticulocyte translation assays to determine activity on eukaryotic ribosomes. Position 2' forms an intramolecular H-bond with O5 of ring II, helping the relative orientations of the two rings with respect to each other. This bond becomes critical for drug activity when a 6' OH substituent is present. Our results point to complex synergistic interactions crucial for aminoglycoside binding and activity.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The kanamycins form an important subgroup of the 4,6-disubstituted 2-deoxystreptamine aminoglycoside antibiotics, comprising kanamycin A, kanamycin B, tobramycin and dibekacin. These compounds interfere with protein synthesis by targeting the ribosomal decoding A site and they differ in the number and location of amino and hydroxy groups of the glucopyranosyl moiety (ring I). We have synthesized kanamycin analogues characterized by subtle variations of the 2' and 6' substituents of ring I. The functional activities of the kanamycins and the synthesized analogues were investigated i) in cell-free translation assays on wild-type and mutant bacterial ribosomes to study drug-target interaction, ii) in MIC assays to assess antibacterial activity, and iii) in rabbit reticulocyte translation assays to determine activity on eukaryotic ribosomes. Position 2' forms an intramolecular H-bond with O5 of ring II, helping the relative orientations of the two rings with respect to each other. This bond becomes critical for drug activity when a 6' OH substituent is present. Our results point to complex synergistic interactions crucial for aminoglycoside binding and activity.
Mertz D, Cui J, Yan Y, Devlin G, Chaubaroux C, Dochter A, Alles R, Lavalle P, Voegel J C, Blencowe A, Auffinger P, Caruso F
Protein capsules assembled via isobutyramide grafts: sequential growth, biofunctionalization, and cellular uptake. Journal Article
In: ACS Nano, vol. 6, no. 9, pp. 7584-7594, 2012, ISBN: 22950440.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Protein capsules assembled via isobutyramide grafts: sequential growth, biofunctionalization, and cellular uptake.},
author = {D Mertz and J Cui and Y Yan and G Devlin and C Chaubaroux and A Dochter and R Alles and P Lavalle and J C Voegel and A Blencowe and P Auffinger and F Caruso},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22950440?dopt=Abstract
http://pubs.acs.org/doi/full/10.1021/nn302024t},
doi = {10.1021/nn302024t},
isbn = {22950440},
year = {2012},
date = {2012-01-01},
journal = {ACS Nano},
volume = {6},
number = {9},
pages = {7584-7594},
abstract = {We report the sequential assembly of proteins via the alternating physical adsorption of human serum albumin (HSA) and chemical grafting with isobutyramide (IBAM) or bromoisobutyramide (BrIBAM) groups. This approach, performed on silica template particles, leads to the formation of noncovalent protein films with controlled growth at the nanometer scale. Further, after template removal, hollow protein capsules with tunable wall thicknesses and high mechanical stability are obtained. The use of BrIBAM, compared to IBAM grafts, leads to significantly thicker capsule walls, highlighting the influence of the bromine atoms in the assembly process, which is discussed in terms of a theoretical model of noncovalent interactions. Another feature of the process is the possibility to functionalize the HSA capsules with other biologically active macromolecules, including enzymes, polysaccharides, or DNA plasmids, demonstrating the versatility of this approach. We also report that BrIBAM-HSA and IBAM-HSA capsules display negligible cytotoxicity in vitro with HeLa cells and that their cellular uptake is dependent on the thickness of the capsule walls. These findings support the potential use of these protein capsules in tailored biological applications such as drug delivery.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
We report the sequential assembly of proteins via the alternating physical adsorption of human serum albumin (HSA) and chemical grafting with isobutyramide (IBAM) or bromoisobutyramide (BrIBAM) groups. This approach, performed on silica template particles, leads to the formation of noncovalent protein films with controlled growth at the nanometer scale. Further, after template removal, hollow protein capsules with tunable wall thicknesses and high mechanical stability are obtained. The use of BrIBAM, compared to IBAM grafts, leads to significantly thicker capsule walls, highlighting the influence of the bromine atoms in the assembly process, which is discussed in terms of a theoretical model of noncovalent interactions. Another feature of the process is the possibility to functionalize the HSA capsules with other biologically active macromolecules, including enzymes, polysaccharides, or DNA plasmids, demonstrating the versatility of this approach. We also report that BrIBAM-HSA and IBAM-HSA capsules display negligible cytotoxicity in vitro with HeLa cells and that their cellular uptake is dependent on the thickness of the capsule walls. These findings support the potential use of these protein capsules in tailored biological applications such as drug delivery.
Louis V L, Despons L, Friedrich A, Martin T, Durrens P, Casarégola S, Neuvéglise C, Fairhead C, Marck C, Cruz J A, Straub M L, Kugler V, Sacerdot C, Uzunov Z, Thierry A, Weiss S, Bleykasten C, Montigny J De, Jacques N, Jung P, Lemaire M, Mallet S, Morel G, Richard G F, Sarkar A, Savel G, Schacherer J, Seret M L, Talla E, Samson G, Jubin C, Poulain J, Vacherie B, Barbe V, Pelletier E, Sherman D J, Westhof E, Weissenbach J, Baret P V, Wincker P, Gaillardin C, Dujon B, Souciet J L
Pichia sorbitophila, an Interspecies Yeast Hybrid, Reveals Early Steps of Genome Resolution After Polyploidization. Journal Article
In: G3 (Bethesda), vol. 2, no. 2, pp. 299-311, 2012, ISBN: 22384408.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Pichia sorbitophila, an Interspecies Yeast Hybrid, Reveals Early Steps of Genome Resolution After Polyploidization.},
author = {V L Louis and L Despons and A Friedrich and T Martin and P Durrens and S Casarégola and C Neuvéglise and C Fairhead and C Marck and J A Cruz and M L Straub and V Kugler and C Sacerdot and Z Uzunov and A Thierry and S Weiss and C Bleykasten and J De Montigny and N Jacques and P Jung and M Lemaire and S Mallet and G Morel and G F Richard and A Sarkar and G Savel and J Schacherer and M L Seret and E Talla and G Samson and C Jubin and J Poulain and B Vacherie and V Barbe and E Pelletier and D J Sherman and E Westhof and J Weissenbach and P V Baret and P Wincker and C Gaillardin and B Dujon and J L Souciet},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22384408?dopt=Abstract},
isbn = {22384408},
year = {2012},
date = {2012-01-01},
journal = {G3 (Bethesda)},
volume = {2},
number = {2},
pages = {299-311},
abstract = {Polyploidization is an important process in the evolution of eukaryotic genomes, but ensuing molecular mechanisms remain to be clarified. Autopolyploidization or whole-genome duplication events frequently are resolved in resulting lineages by the loss of single genes from most duplicated pairs, causing transient gene dosage imbalance and accelerating speciation through meiotic infertility. Allopolyploidization or formation of interspecies hybrids raises the problem of genetic incompatibility (Bateson-Dobzhansky-Muller effect) and may be resolved by the accumulation of mutational changes in resulting lineages. In this article, we show that an osmotolerant yeast species, Pichia sorbitophila, recently isolated in a concentrated sorbitol solution in industry, illustrates this last situation. Its genome is a mosaic of homologous and homeologous chromosomes, or parts thereof, that corresponds to a recently formed hybrid in the process of evolution. The respective parental contributions to this genome were characterized using existing variations in GC content. The genomic changes that occurred during the short period since hybrid formation were identified (e.g., loss of heterozygosity, unilateral loss of rDNA, reciprocal exchange) and distinguished from those undergone by the two parental genomes after separation from their common ancestor (i.e., NUMT (NUclear sequences of MiTochondrial origin) insertions, gene acquisitions, gene location movements, reciprocal translocation). We found that the physiological characteristics of this new yeast species are determined by specific but unequal contributions of its two parents, one of which could be identified as very closely related to an extant Pichia farinosa strain.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Polyploidization is an important process in the evolution of eukaryotic genomes, but ensuing molecular mechanisms remain to be clarified. Autopolyploidization or whole-genome duplication events frequently are resolved in resulting lineages by the loss of single genes from most duplicated pairs, causing transient gene dosage imbalance and accelerating speciation through meiotic infertility. Allopolyploidization or formation of interspecies hybrids raises the problem of genetic incompatibility (Bateson-Dobzhansky-Muller effect) and may be resolved by the accumulation of mutational changes in resulting lineages. In this article, we show that an osmotolerant yeast species, Pichia sorbitophila, recently isolated in a concentrated sorbitol solution in industry, illustrates this last situation. Its genome is a mosaic of homologous and homeologous chromosomes, or parts thereof, that corresponds to a recently formed hybrid in the process of evolution. The respective parental contributions to this genome were characterized using existing variations in GC content. The genomic changes that occurred during the short period since hybrid formation were identified (e.g., loss of heterozygosity, unilateral loss of rDNA, reciprocal exchange) and distinguished from those undergone by the two parental genomes after separation from their common ancestor (i.e., NUMT (NUclear sequences of MiTochondrial origin) insertions, gene acquisitions, gene location movements, reciprocal translocation). We found that the physiological characteristics of this new yeast species are determined by specific but unequal contributions of its two parents, one of which could be identified as very closely related to an extant Pichia farinosa strain.
Leontis N, Westhof E
Modeling RNA Molecules Book Chapter
In: Leontis, N; Westhof, E (Ed.): RNA 3D Structure Analysis and Predication, pp. 5-17, Springer, 2012.
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@inbook{,
title = {Modeling RNA Molecules},
author = {N Leontis and E Westhof},
editor = {N Leontis and E Westhof},
url = {http://link.springer.com/chapter/10.1007/978-3-642-25740-7_2},
doi = {10.1007/978-3-642-25740-7_2},
year = {2012},
date = {2012-01-01},
booktitle = {RNA 3D Structure Analysis and Predication},
pages = {5-17},
publisher = {Springer},
series = {Nucleic Acids and Molecular Biology},
abstract = {A primary activity of scientific work is the construction of models to represent the nature and workings of phenomena we observe in the world around us. Models that represent the molecular components of living system in three dimensions (3D) and at atomic resolution are highly valued in molecular and structural biology. For example, the decipherment of the 3D structures of ribosomes, the complex protein-synthesizing nanomachines of the cell, represents a tremendous achievement, recently recognized with the Nobel Prize in Chemistry (http://nobelprize.org/nobel_prizes/chemistry/laureates/2009/). Nonetheless, this phenomenal success is tempered by the realization that even now, over 10 years after the first ribosome structures were solved, we still do not understand fully several aspects of their functioning. For all who have grappled with the complexities of ribosome structures, Richard Feynmannﾒs pithy statement, ﾓWhat I cannot create, I do not understand,ﾔ rings especially true (Hawking 2001). This physics-based realization contrasts with another point of view of modeling. To paraphrase R. W. Hamming, who said, ﾓThe purpose of computing is insight, not numbersﾔ (Hamming 1971), we should remember that the purpose of molecular modeling is functional insight, not detailed atomic models per se. Therefore, as we seek to improve our abilities to construct 3D models for molecules for which we do not yet have experimental atomic-resolution structures, we should bear in mind that it may not be necessary to achieve some arbitrary precision in the atomic coordinates to provide insight into biological function. Rather, we should think carefully to identify those predicted features that yield important insights},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {inbook}
}
A primary activity of scientific work is the construction of models to represent the nature and workings of phenomena we observe in the world around us. Models that represent the molecular components of living system in three dimensions (3D) and at atomic resolution are highly valued in molecular and structural biology. For example, the decipherment of the 3D structures of ribosomes, the complex protein-synthesizing nanomachines of the cell, represents a tremendous achievement, recently recognized with the Nobel Prize in Chemistry (http://nobelprize.org/nobel_prizes/chemistry/laureates/2009/). Nonetheless, this phenomenal success is tempered by the realization that even now, over 10 years after the first ribosome structures were solved, we still do not understand fully several aspects of their functioning. For all who have grappled with the complexities of ribosome structures, Richard Feynmannﾒs pithy statement, ﾓWhat I cannot create, I do not understand,ﾔ rings especially true (Hawking 2001). This physics-based realization contrasts with another point of view of modeling. To paraphrase R. W. Hamming, who said, ﾓThe purpose of computing is insight, not numbersﾔ (Hamming 1971), we should remember that the purpose of molecular modeling is functional insight, not detailed atomic models per se. Therefore, as we seek to improve our abilities to construct 3D models for molecules for which we do not yet have experimental atomic-resolution structures, we should bear in mind that it may not be necessary to achieve some arbitrary precision in the atomic coordinates to provide insight into biological function. Rather, we should think carefully to identify those predicted features that yield important insights
Lamiable A, Barth D, Denise A, Quessette F, Vial S, Westhof E
Automated prediction of three-way junction topological families in RNA secondary structures. Journal Article
In: Comput Biol Chem, vol. 37, pp. 1-5, 2012, ISBN: 22326420, (Available online 11 January 2012.).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Automated prediction of three-way junction topological families in RNA secondary structures.},
author = {A Lamiable and D Barth and A Denise and F Quessette and S Vial and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22326420},
doi = {10.1016/j.compbiolchem.2011.11.001},
isbn = {22326420},
year = {2012},
date = {2012-01-01},
journal = {Comput Biol Chem},
volume = {37},
pages = {1-5},
abstract = {We present an algorithm for automatically predicting the topological family of any RNA three-way junction, given only the information from the secondary structure: the sequence and the Watson-Crick pairings. The parameters of the algorithm have been determined on a data set of 33 three-way junctions whose 3D conformation is known. We applied the algorithm on 53 other junctions and compared the predictions to the real shape of those junctions. We show that the correct answer is selected out of nine possible configurations 64% of the time. Additionally, these results are noticeably improved if homology information is used. The resulting software, Cartaj, is available online and downloadable (with source) at: http://cartaj.lri.fr.},
note = {Available online 11 January 2012.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
We present an algorithm for automatically predicting the topological family of any RNA three-way junction, given only the information from the secondary structure: the sequence and the Watson-Crick pairings. The parameters of the algorithm have been determined on a data set of 33 three-way junctions whose 3D conformation is known. We applied the algorithm on 53 other junctions and compared the predictions to the real shape of those junctions. We show that the correct answer is selected out of nine possible configurations 64% of the time. Additionally, these results are noticeably improved if homology information is used. The resulting software, Cartaj, is available online and downloadable (with source) at: http://cartaj.lri.fr.
Demeshkina N, Jenner L, Westhof E, Yusupov M, Yusupova G
A new understanding of the decoding principle on the ribosome. Journal Article
In: Nature, vol. 484, no. 7393, pp. 256-259, 2012, ISBN: 22437501, (Published online 21 March 2012).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {A new understanding of the decoding principle on the ribosome.},
author = {N Demeshkina and L Jenner and E Westhof and M Yusupov and G Yusupova},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22437501?dopt=Abstract},
doi = {10.1038/nature10913},
isbn = {22437501},
year = {2012},
date = {2012-01-01},
journal = {Nature},
volume = {484},
number = {7393},
pages = {256-259},
abstract = {During protein synthesis, the ribosome accurately selects transfer RNAs (tRNAs) in accordance with the messenger RNA (mRNA) triplet in the decoding centre. tRNA selection is initiated by elongation factor Tu, which delivers tRNA to the aminoacyl tRNA-binding site (A site) and hydrolyses GTP upon establishing codon-anticodon interactions in the decoding centre. At the following proofreading step the ribosome re-examines the tRNA and rejects it if it does not match the A codon. It was suggested that universally conserved G530, A1492 and A1493 of 16S ribosomal RNA, critical for tRNA binding in the A site, actively monitor cognate tRNA, and that recognition of the correct codon-anticodon duplex induces an overall ribosome conformational change (domain closure). Here we propose an integrated mechanism for decoding based on six X-ray structures of the 70S ribosome determined at 3.1-3.4 Å resolution, modelling cognate or near-cognate states of the decoding centre at the proofreading step. We show that the 30S subunit undergoes an identical domain closure upon binding of either cognate or near-cognate tRNA. This conformational change of the 30S subunit forms a decoding centre that constrains the mRNA in such a way that the first two nucleotides of the A codon are limited to form Watson-Crick base pairs. When U·G and G·U mismatches, generally considered to form wobble base pairs, are at the first or second codon-anticodon position, the decoding centre forces this pair to adopt the geometry close to that of a canonical C·G pair. This by itself, or with distortions in the codon-anticodon mini-helix and the anticodon loop, causes the near-cognate tRNA to dissociate from the ribosome.},
note = {Published online 21 March 2012},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
During protein synthesis, the ribosome accurately selects transfer RNAs (tRNAs) in accordance with the messenger RNA (mRNA) triplet in the decoding centre. tRNA selection is initiated by elongation factor Tu, which delivers tRNA to the aminoacyl tRNA-binding site (A site) and hydrolyses GTP upon establishing codon-anticodon interactions in the decoding centre. At the following proofreading step the ribosome re-examines the tRNA and rejects it if it does not match the A codon. It was suggested that universally conserved G530, A1492 and A1493 of 16S ribosomal RNA, critical for tRNA binding in the A site, actively monitor cognate tRNA, and that recognition of the correct codon-anticodon duplex induces an overall ribosome conformational change (domain closure). Here we propose an integrated mechanism for decoding based on six X-ray structures of the 70S ribosome determined at 3.1-3.4 Å resolution, modelling cognate or near-cognate states of the decoding centre at the proofreading step. We show that the 30S subunit undergoes an identical domain closure upon binding of either cognate or near-cognate tRNA. This conformational change of the 30S subunit forms a decoding centre that constrains the mRNA in such a way that the first two nucleotides of the A codon are limited to form Watson-Crick base pairs. When U·G and G·U mismatches, generally considered to form wobble base pairs, are at the first or second codon-anticodon position, the decoding centre forces this pair to adopt the geometry close to that of a canonical C·G pair. This by itself, or with distortions in the codon-anticodon mini-helix and the anticodon loop, causes the near-cognate tRNA to dissociate from the ribosome.
Meyer M, Westhof E, Masquida B
A structural module in RNase P expands the variety of RNA kinks. Journal Article
In: RNA Biol, vol. 9, no. 3, pp. 254-260, 2012, ISBN: 22336704.
Abstract | Links | BibTeX | Tags: Kink-turn RNA module RNA motif RNA structure RNase P Structural alignment, Unité ARN, WESTHOF
@article{,
title = {A structural module in RNase P expands the variety of RNA kinks.},
author = {M Meyer and E Westhof and B Masquida},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22336704},
isbn = {22336704},
year = {2012},
date = {2012-01-01},
journal = {RNA Biol},
volume = {9},
number = {3},
pages = {254-260},
abstract = {RNA structures are built from recurrent modules that can be identified by structural and comparative sequence analysis. In order to assemble sets of helices in compact architectures, modules that introduce bends and kinks are necessary. Among such modules, kink-turns form an important family that presents sequence and structural characteristics. Here, we describe an internal loop in the bacterial type A RNase P RNA that sets helices bound at the junctions exactly in the same relative positions as in kink-turns but without the structural signatures typical of kink-turns. Our work suggests that identifying a structural module in a subset of RNA sequences constitutes a strategy to identify distinct sequential motifs sharing common structural characteristics.},
keywords = {Kink-turn RNA module RNA motif RNA structure RNase P Structural alignment, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
RNA structures are built from recurrent modules that can be identified by structural and comparative sequence analysis. In order to assemble sets of helices in compact architectures, modules that introduce bends and kinks are necessary. Among such modules, kink-turns form an important family that presents sequence and structural characteristics. Here, we describe an internal loop in the bacterial type A RNase P RNA that sets helices bound at the junctions exactly in the same relative positions as in kink-turns but without the structural signatures typical of kink-turns. Our work suggests that identifying a structural module in a subset of RNA sequences constitutes a strategy to identify distinct sequential motifs sharing common structural characteristics.
Auffinger P
Ions in molecular dynamics simulations of RNA systems. Book Chapter
In: Leontis, N; Westhof, E (Ed.): RNA 3D Structure Analysis and Prediction (Nucleic Acids and Molecular Biology), vol. 27, pp. 299-318, Springer, Berlin, 2012.
Abstract | Links | BibTeX | Tags: Molecular dynamics simulation Crystallography RNA DNA Solvation Hydration Monovalent cation Divalent cation Sodium Potassium Magnesium Na+ K+ Mg2+, Unité ARN, WESTHOF
@inbook{,
title = {Ions in molecular dynamics simulations of RNA systems.},
author = {P Auffinger},
editor = {N Leontis and E Westhof},
url = {http://www.springerlink.com/content/r770wvrn0m200t04},
doi = {10.1007/978-3-642-25740-7_14},
year = {2012},
date = {2012-01-01},
booktitle = {RNA 3D Structure Analysis and Prediction (Nucleic Acids and Molecular Biology)},
volume = {27},
pages = {299-318},
publisher = {Springer, Berlin},
abstract = {Ions and water molecules are intricately associated with biomolecular systems and play important structural and functional roles that are still not well understood. For RNA systems, the functions of these ions are not limited to the neutralization of the charges carried by the polyanionic backbone, since they also bind to very specific locations of the RNA 3D fold. Hence, it is essential to include them with the greatest possible accuracy in 3D structural models and especially in molecular dynamics (MD) simulations. This review aims at describing some of the successes achieved in the modeling of monovalent and divalent ions in RNA systems, as well as to highlight important deficiencies of current force fields and MD techniques that represent important challenges for future development.},
keywords = {Molecular dynamics simulation Crystallography RNA DNA Solvation Hydration Monovalent cation Divalent cation Sodium Potassium Magnesium Na+ K+ Mg2+, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {inbook}
}
Ions and water molecules are intricately associated with biomolecular systems and play important structural and functional roles that are still not well understood. For RNA systems, the functions of these ions are not limited to the neutralization of the charges carried by the polyanionic backbone, since they also bind to very specific locations of the RNA 3D fold. Hence, it is essential to include them with the greatest possible accuracy in 3D structural models and especially in molecular dynamics (MD) simulations. This review aims at describing some of the successes achieved in the modeling of monovalent and divalent ions in RNA systems, as well as to highlight important deficiencies of current force fields and MD techniques that represent important challenges for future development.
Romilly C, Chevalier C, Marzi S, Masquida B, Geissmann T, Vandenesch F, Westhof E, Romby P
Loop-loop interactions involved in antisense regulation are processed by the endoribonuclease III in Staphylococcus aureus. Journal Article
In: RNA Biol, vol. 9, no. 12, pp. 1461-1472, 2012, ISBN: 23134978.
Abstract | Links | BibTeX | Tags: ROMBY, Unité ARN, WESTHOF
@article{,
title = {Loop-loop interactions involved in antisense regulation are processed by the endoribonuclease III in Staphylococcus aureus.},
author = {C Romilly and C Chevalier and S Marzi and B Masquida and T Geissmann and F Vandenesch and E Westhof and P Romby},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23134978?dopt=Abstract},
doi = {10.4161/rna.22710},
isbn = {23134978},
year = {2012},
date = {2012-01-01},
journal = {RNA Biol},
volume = {9},
number = {12},
pages = {1461-1472},
abstract = {The endoribonuclease III (RNase III) belongs to the enzyme family known to process double-stranded RNAs. Staphylococcus aureus RNase III was shown to regulate, in concert with the quorum sensing induced RNAIII, the degradation of several mRNAs encoding virulence factors and the transcriptional repressor of toxins Rot. Two of the mRNA-RNAIII complexes involve fully base paired loop-loop interactions with similar sequences that are cleaved by RNase III at a unique position. We show here that the sequence of the base pairs within the loop-loop interaction was not critical for RNase III cleavage, but that the co-axial stacking of three consecutive helices provides an ideal topology for RNase III recognition. In contrast, RNase III induces several strong cleavages in a regular helix, which carries a sequence similar to the loop-loop interaction. The introduction of a bulged loop that interrupts the regular helix restrains the number of cleavages. This work shows that S. aureus RNase III is able to bind and cleave a variety of RNA-mRNA substrates, and that specific structure elements direct the action of RNase III.},
keywords = {ROMBY, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The endoribonuclease III (RNase III) belongs to the enzyme family known to process double-stranded RNAs. Staphylococcus aureus RNase III was shown to regulate, in concert with the quorum sensing induced RNAIII, the degradation of several mRNAs encoding virulence factors and the transcriptional repressor of toxins Rot. Two of the mRNA-RNAIII complexes involve fully base paired loop-loop interactions with similar sequences that are cleaved by RNase III at a unique position. We show here that the sequence of the base pairs within the loop-loop interaction was not critical for RNase III cleavage, but that the co-axial stacking of three consecutive helices provides an ideal topology for RNase III recognition. In contrast, RNase III induces several strong cleavages in a regular helix, which carries a sequence similar to the loop-loop interaction. The introduction of a bulged loop that interrupts the regular helix restrains the number of cleavages. This work shows that S. aureus RNase III is able to bind and cleave a variety of RNA-mRNA substrates, and that specific structure elements direct the action of RNase III.
Westhof E
Ribozymes, catalytically active RNA molecules. Introduction. Book Chapter
In: Hartig, J S (Ed.): Ribozymes: Methods and Protocols, vol. 848, pp. 1-4, Springer Protocols, Humana Press, 2012, ISBN: 22315059, (Methods in molecular biology (Clifton, N.J.)).
Abstract | Links | BibTeX | Tags: RNA catalysis Ribozyme Hammerhead, Unité ARN, WESTHOF, WESTHOF RNA catalysis Ribozyme Hammerhead Overview
@inbook{,
title = {Ribozymes, catalytically active RNA molecules. Introduction.},
author = {E Westhof},
editor = {J S Hartig},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22315059},
doi = {10.1007/978-1-61779-545-9_1},
isbn = {22315059},
year = {2012},
date = {2012-01-01},
booktitle = {Ribozymes: Methods and Protocols},
volume = {848},
pages = {1-4},
publisher = {Springer Protocols, Humana Press},
series = {Methods in Molecular Biology},
abstract = {It is now about 30 years since ribozymes, catalytically active RNA molecules, were discovered. Although the chemical versatility of RNA does not come close to that of proteins, the chemical properties of nucleic acid systems are nevertheless thoroughly exploited in biological systems, leading to diverse ways of accelerating chemical reactions. Ribozymes are truly fascinating biological molecules. After all, is catalytic RNA an accident of life or, instead, is life an accident of catalytic RNA?},
note = {Methods in molecular biology (Clifton, N.J.)},
keywords = {RNA catalysis Ribozyme Hammerhead, Unité ARN, WESTHOF, WESTHOF RNA catalysis Ribozyme Hammerhead Overview},
pubstate = {published},
tppubtype = {inbook}
}
It is now about 30 years since ribozymes, catalytically active RNA molecules, were discovered. Although the chemical versatility of RNA does not come close to that of proteins, the chemical properties of nucleic acid systems are nevertheless thoroughly exploited in biological systems, leading to diverse ways of accelerating chemical reactions. Ribozymes are truly fascinating biological molecules. After all, is catalytic RNA an accident of life or, instead, is life an accident of catalytic RNA?
Leontis N, Westhof E (Ed.)
RNA 3D Structure Analysis and Prediction Book
Springer, Berlin, 2012.
BibTeX | Tags: Unité ARN, WESTHOF
@book{,
title = {RNA 3D Structure Analysis and Prediction},
editor = {N Leontis and E Westhof},
year = {2012},
date = {2012-01-01},
publisher = {Springer, Berlin},
series = {Nucleic Acids and Molecular Biology},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {book}
}
Cruz J A, Blanchet M F, Boniecki M, Bujnicki J M, Chen S J, Cao S, Das R, Ding F, Dokholyan N V, Flores S C, Huang L, Lavender C A, Lisi V, Major F, Mikolajczak K, Patel D J, Philips A, Puton T, Santalucia J, Sijenyi F, Hermann T, Rother K, Rother M, Serganov A, Skorupski M, Soltysinski T, Sripakdeevong P, Tuszynska I, Weeks K M, Waldsich C, Wildauer M, Leontis N B, Westhof E
RNA-Puzzles: A CASP-like evaluation of RNA three-dimensional structure prediction. Journal Article
In: RNA, vol. 18, no. 4, pp. 610-625, 2012, ISBN: 2236129, (Published in Advance February 23, 2012).
Abstract | Links | BibTeX | Tags: 3D prediction Bioinformatics Force fields Structure, Unité ARN, WESTHOF, WESTHOF 3D prediction Bioinformatics Force fields Structure
@article{,
title = {RNA-Puzzles: A CASP-like evaluation of RNA three-dimensional structure prediction.},
author = {J A Cruz and M F Blanchet and M Boniecki and J M Bujnicki and S J Chen and S Cao and R Das and F Ding and N V Dokholyan and S C Flores and L Huang and C A Lavender and V Lisi and F Major and K Mikolajczak and D J Patel and A Philips and T Puton and J Santalucia and F Sijenyi and T Hermann and K Rother and M Rother and A Serganov and M Skorupski and T Soltysinski and P Sripakdeevong and I Tuszynska and K M Weeks and C Waldsich and M Wildauer and N B Leontis and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22361291?dopt=Abstract},
doi = {10.1261/rna.031054.111},
isbn = {2236129},
year = {2012},
date = {2012-01-01},
journal = {RNA},
volume = {18},
number = {4},
pages = {610-625},
abstract = {We report the results of a first, collective, blind experiment in RNA three-dimensional (3D) structure prediction, encompassing three prediction puzzles. The goals are to assess the leading edge of RNA structure prediction techniques; compare existing methods and tools; and evaluate their relative strengths, weaknesses, and limitations in terms of sequence length and structural complexity. The results should give potential users insight into the suitability of available methods for different applications and facilitate efforts in the RNA structure prediction community in ongoing efforts to improve prediction tools. We also report the creation of an automated evaluation pipeline to facilitate the analysis of future RNA structure prediction exercises.},
note = {Published in Advance February 23, 2012},
keywords = {3D prediction Bioinformatics Force fields Structure, Unité ARN, WESTHOF, WESTHOF 3D prediction Bioinformatics Force fields Structure},
pubstate = {published},
tppubtype = {article}
}
We report the results of a first, collective, blind experiment in RNA three-dimensional (3D) structure prediction, encompassing three prediction puzzles. The goals are to assess the leading edge of RNA structure prediction techniques; compare existing methods and tools; and evaluate their relative strengths, weaknesses, and limitations in terms of sequence length and structural complexity. The results should give potential users insight into the suitability of available methods for different applications and facilitate efforts in the RNA structure prediction community in ongoing efforts to improve prediction tools. We also report the creation of an automated evaluation pipeline to facilitate the analysis of future RNA structure prediction exercises.
Westhof E, Auffinger P
Transfer RNA structure Book Chapter
In: Encyclopedia of Life Sciences, John Wiley & Sons, 2012.
Abstract | Links | BibTeX | Tags: transfer ribonucleic acid tRNA cloverleaf structure wobble hypothesis anticodon WatsonCrick pairs non-WatsonCrick pairs hydrogen bond Hoogsteen pairs dynamics solvation magnesium, Unité ARN, WESTHOF
@inbook{,
title = {Transfer RNA structure},
author = {E Westhof and P Auffinger},
url = {http://www.els.net/WileyCDA/ElsArticle/refId-a0000527.html},
doi = {10.1002/9780470015902.a0000527.pub2},
year = {2012},
date = {2012-01-01},
booktitle = {Encyclopedia of Life Sciences},
publisher = {John Wiley & Sons},
abstract = {Transfer ribonucleic acid (tRNA) molecules that participate
in the elongation step of protein synthesis on the
ribosome have a conserved secondary structure, known as
the cloverleaf, and fold into a common three-dimensional
architecture. The conservation of the global L-shaped 3D
fold is assessed by the more than 100 available crystal
structures showing tRNAs in native states or in complexes
where tRNAs are bound to various interacting systems
such as cognate synthetases, editing, modification and
processing enzymes or full ribosomes. These tRNA crystal
structures display awhole range of structural adaptability
features encoded in their sequence and underlying their
various functions. Thus, as the number of available structural
data expands, the concept of a unique tRNA structure
fades out for that of an ensemble of interconnected
and environmentally dependant tRNA structures.},
keywords = {transfer ribonucleic acid tRNA cloverleaf structure wobble hypothesis anticodon WatsonCrick pairs non-WatsonCrick pairs hydrogen bond Hoogsteen pairs dynamics solvation magnesium, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {inbook}
}
Transfer ribonucleic acid (tRNA) molecules that participate
in the elongation step of protein synthesis on the
ribosome have a conserved secondary structure, known as
the cloverleaf, and fold into a common three-dimensional
architecture. The conservation of the global L-shaped 3D
fold is assessed by the more than 100 available crystal
structures showing tRNAs in native states or in complexes
where tRNAs are bound to various interacting systems
such as cognate synthetases, editing, modification and
processing enzymes or full ribosomes. These tRNA crystal
structures display awhole range of structural adaptability
features encoded in their sequence and underlying their
various functions. Thus, as the number of available structural
data expands, the concept of a unique tRNA structure
fades out for that of an ensemble of interconnected
and environmentally dependant tRNA structures.
in the elongation step of protein synthesis on the
ribosome have a conserved secondary structure, known as
the cloverleaf, and fold into a common three-dimensional
architecture. The conservation of the global L-shaped 3D
fold is assessed by the more than 100 available crystal
structures showing tRNAs in native states or in complexes
where tRNAs are bound to various interacting systems
such as cognate synthetases, editing, modification and
processing enzymes or full ribosomes. These tRNA crystal
structures display awhole range of structural adaptability
features encoded in their sequence and underlying their
various functions. Thus, as the number of available structural
data expands, the concept of a unique tRNA structure
fades out for that of an ensemble of interconnected
and environmentally dependant tRNA structures.
2011
Westhof E, Masquida B, Jossinet F
Predicting and modeling RNA architecture Journal Article
In: Cold Spring Harb Perspect Biol, vol. 3, no. 2, pp. 309-320, 2011, ISSN: 1943-0264 (Electronic), (Westhof, Eric Masquida, Benoit Jossinet, Fabrice United States Cold Spring Harbor perspectives in biology Cold Spring Harb Perspect Biol. 2011 Feb 1;3(2). pii: a003632. doi: 10.1101/cshperspect.a003632.).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Predicting and modeling RNA architecture},
author = {E Westhof and B Masquida and F Jossinet},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20504963},
doi = {10.1101/cshperspect.a003632},
issn = {1943-0264 (Electronic)},
year = {2011},
date = {2011-01-01},
journal = {Cold Spring Harb Perspect Biol},
volume = {3},
number = {2},
pages = {309-320},
abstract = {A general approach for modeling the architecture of large and structured RNA molecules is described. The method exploits the modularity and the hierarchical folding of RNA architecture that is viewed as the assembly of preformed double-stranded helices defined by Watson-Crick base pairs and RNA modules maintained by non-Watson-Crick base pairs. Despite the extensive molecular neutrality observed in RNA structures, specificity in RNA folding is achieved through global constraints like lengths of helices, coaxiality of helical stacks, and structures adopted at the junctions of helices. The Assemble integrated suite of computer tools allows for sequence and structure analysis as well as interactive modeling by homology or ab initio assembly with possibilities for fitting within electronic density maps. The local key role of non-Watson-Crick pairs guides RNA architecture formation and offers metrics for assessing the accuracy of three-dimensional models in a more useful way than usual root mean square deviation (RMSD) values.},
note = {Westhof, Eric
Masquida, Benoit
Jossinet, Fabrice
United States
Cold Spring Harbor perspectives in biology
Cold Spring Harb Perspect Biol. 2011 Feb 1;3(2). pii: a003632. doi: 10.1101/cshperspect.a003632.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
A general approach for modeling the architecture of large and structured RNA molecules is described. The method exploits the modularity and the hierarchical folding of RNA architecture that is viewed as the assembly of preformed double-stranded helices defined by Watson-Crick base pairs and RNA modules maintained by non-Watson-Crick base pairs. Despite the extensive molecular neutrality observed in RNA structures, specificity in RNA folding is achieved through global constraints like lengths of helices, coaxiality of helical stacks, and structures adopted at the junctions of helices. The Assemble integrated suite of computer tools allows for sequence and structure analysis as well as interactive modeling by homology or ab initio assembly with possibilities for fitting within electronic density maps. The local key role of non-Watson-Crick pairs guides RNA architecture formation and offers metrics for assessing the accuracy of three-dimensional models in a more useful way than usual root mean square deviation (RMSD) values.
Westhof E, Fritsch V
The Endless Subtleties of RNA-Protein Complexes. Journal Article
In: Structure, vol. 19, no. 7, pp. 902-903, 2011, ISSN: 1878-4186, (DOI:10.1016/j.str.2011.06.006).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {The Endless Subtleties of RNA-Protein Complexes.},
author = {E Westhof and V Fritsch},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21742256},
issn = {1878-4186},
year = {2011},
date = {2011-01-01},
journal = {Structure},
volume = {19},
number = {7},
pages = {902-903},
abstract = {New NMR structures of complexes between double-strand RNA binding domains and their RNA hairpin substrates reported by Wang et al. in this issue of Structure reveal striking adaptations in both the protein recognition element and in the RNA.},
note = {DOI:10.1016/j.str.2011.06.006},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
New NMR structures of complexes between double-strand RNA binding domains and their RNA hairpin substrates reported by Wang et al. in this issue of Structure reveal striking adaptations in both the protein recognition element and in the RNA.
Theil E C, Westhof E
New dimensions of RNA in molecular recognition and catalysis. Journal Article
In: Acc Chem Res, vol. 44, no. 12, pp. 1255-1256, 2011, ISBN: 22181677.
Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {New dimensions of RNA in molecular recognition and catalysis.},
author = {E C Theil and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22181677},
isbn = {22181677},
year = {2011},
date = {2011-01-01},
journal = {Acc Chem Res},
volume = {44},
number = {12},
pages = {1255-1256},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Wright J E, Gaidatzis D, Senften M, Farley B M, Westhof E, Ryder S P, Ciosk R
A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1 Journal Article
In: EMBO J, vol. 30, no. 3, pp. 533-545, 2011, ISSN: 1460-2075 (Electronic) 0261-4189 (Linking), (Wright, Jane E Gaidatzis, Dimos Senften, Mathias Farley, Brian M Westhof, Eric Ryder, Sean P Ciosk, Rafal GM081422/GM/NIGMS NIH HHS/United States R01 GM081422-01A1/GM/NIGMS NIH HHS/United States R01 GM081422-02/GM/NIGMS NIH HHS/United States R01 GM081422-03/GM/NIGMS NIH HHS/United States R01 GM081422-04/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England The EMBO journal EMBO J. 2011 Feb 2;30(3):533-45. Epub 2010 Dec 17.).
Abstract | Links | BibTeX | Tags: Animals Binding, Biological Protein Interaction Domains and Motifs/*genetics RNA, Competitive Caenorhabditis elegans/*genetics/metabolism Caenorhabditis elegans Proteins/*metabolism Computational Biology/methods Gene Regulatory Networks/*genetics Immunoprecipitation Microarray Analysis *Models, Messenger/*metabolism RNA-Binding Proteins/*metabolism, Unité ARN, WESTHOF, WESTHOF Animals Binding
@article{,
title = {A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1},
author = {J E Wright and D Gaidatzis and M Senften and B M Farley and E Westhof and S P Ryder and R Ciosk},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21169991},
doi = {10.1038/emboj.2010.334},
issn = {1460-2075 (Electronic) 0261-4189 (Linking)},
year = {2011},
date = {2011-01-01},
journal = {EMBO J},
volume = {30},
number = {3},
pages = {533-545},
abstract = {RNA-binding proteins (RBPs) are critical regulators of gene expression. To understand and predict the outcome of RBP-mediated regulation a comprehensive analysis of their interaction with RNA is necessary. The signal transduction and activation of RNA (STAR) family of RBPs includes developmental regulators and tumour suppressors such as Caenorhabditis elegans GLD-1, which is a key regulator of germ cell development. To obtain a comprehensive picture of GLD-1 interactions with the transcriptome, we identified GLD-1-associated mRNAs by RNA immunoprecipitation followed by microarray detection. Based on the computational analysis of these mRNAs we generated a predictive model, where GLD-1 association with mRNA is determined by the strength and number of 7-mer GLD-1-binding motifs (GBMs) within UTRs. We verified this quantitative model both in vitro, by competition GLD-1/GBM-binding experiments to determine relative affinity, and in vivo, by 'transplantation' experiments, where 'weak' and 'strong' GBMs imposed translational repression of increasing strength on a non-target mRNA. This study demonstrates that transcriptome-wide identification of RBP mRNA targets combined with quantitative computational analysis can generate highly predictive models of post-transcriptional regulatory networks.},
note = {Wright, Jane E
Gaidatzis, Dimos
Senften, Mathias
Farley, Brian M
Westhof, Eric
Ryder, Sean P
Ciosk, Rafal
GM081422/GM/NIGMS NIH HHS/United States
R01 GM081422-01A1/GM/NIGMS NIH HHS/United States
R01 GM081422-02/GM/NIGMS NIH HHS/United States
R01 GM081422-03/GM/NIGMS NIH HHS/United States
R01 GM081422-04/GM/NIGMS NIH HHS/United States
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
England
The EMBO journal
EMBO J. 2011 Feb 2;30(3):533-45. Epub 2010 Dec 17.},
keywords = {Animals Binding, Biological Protein Interaction Domains and Motifs/*genetics RNA, Competitive Caenorhabditis elegans/*genetics/metabolism Caenorhabditis elegans Proteins/*metabolism Computational Biology/methods Gene Regulatory Networks/*genetics Immunoprecipitation Microarray Analysis *Models, Messenger/*metabolism RNA-Binding Proteins/*metabolism, Unité ARN, WESTHOF, WESTHOF Animals Binding},
pubstate = {published},
tppubtype = {article}
}
RNA-binding proteins (RBPs) are critical regulators of gene expression. To understand and predict the outcome of RBP-mediated regulation a comprehensive analysis of their interaction with RNA is necessary. The signal transduction and activation of RNA (STAR) family of RBPs includes developmental regulators and tumour suppressors such as Caenorhabditis elegans GLD-1, which is a key regulator of germ cell development. To obtain a comprehensive picture of GLD-1 interactions with the transcriptome, we identified GLD-1-associated mRNAs by RNA immunoprecipitation followed by microarray detection. Based on the computational analysis of these mRNAs we generated a predictive model, where GLD-1 association with mRNA is determined by the strength and number of 7-mer GLD-1-binding motifs (GBMs) within UTRs. We verified this quantitative model both in vitro, by competition GLD-1/GBM-binding experiments to determine relative affinity, and in vivo, by 'transplantation' experiments, where 'weak' and 'strong' GBMs imposed translational repression of increasing strength on a non-target mRNA. This study demonstrates that transcriptome-wide identification of RBP mRNA targets combined with quantitative computational analysis can generate highly predictive models of post-transcriptional regulatory networks.
Szychowski J, Kondo J, Zahr O, Auclair K, Westhof E, Hanessian S, Keillor J W
Inhibition of Aminoglycoside-Deactivating Enzymes APH(3')-IIIa and AAC(6')-Ii by Amphiphilic Paromomycin O2''-Ether Analogues. Journal Article
In: ChemMedChem, vol. 6, no. 11, pp. 1961-1966, 2011, ISBN: 21905229, (Article first published online: 8 SEP 2011).
Abstract | Links | BibTeX | Tags: Aminoglycosides Antibacterial agents Antibiotics APH(3′)-IIIa Drug discovery Paromomycin, Unité ARN, WESTHOF
@article{,
title = {Inhibition of Aminoglycoside-Deactivating Enzymes APH(3')-IIIa and AAC(6')-Ii by Amphiphilic Paromomycin O2''-Ether Analogues.},
author = {J Szychowski and J Kondo and O Zahr and K Auclair and E Westhof and S Hanessian and J W Keillor},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21905229},
doi = {10.1002/cmdc.201100346},
isbn = {21905229},
year = {2011},
date = {2011-01-01},
journal = {ChemMedChem},
volume = {6},
number = {11},
pages = {1961-1966},
abstract = {Paromomycin analogue activity: Novel amphiphilic aminoglycosides are shown to inhibit clinically relevant deactivating enzymes, without undergoing significant deactivation themselves.},
note = {Article first published online: 8 SEP 2011},
keywords = {Aminoglycosides Antibacterial agents Antibiotics APH(3′)-IIIa Drug discovery Paromomycin, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Paromomycin analogue activity: Novel amphiphilic aminoglycosides are shown to inhibit clinically relevant deactivating enzymes, without undergoing significant deactivation themselves.
Masquida B, Westhof E
RNase P: At last, the key finds its lock. Journal Article
In: RNA, vol. 17, no. 9, pp. 1615-1618, 2011, ISBN: 21803972.
Abstract | Links | BibTeX | Tags: RNase P Multiple-turnover ribozyme RNARNA interactions Molecular evolution Crystallography, Unité ARN, WESTHOF
@article{,
title = {RNase P: At last, the key finds its lock.},
author = {B Masquida and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21803972},
doi = {10.1261/rna.2841511},
isbn = {21803972},
year = {2011},
date = {2011-01-01},
journal = {RNA},
volume = {17},
number = {9},
pages = {1615-1618},
abstract = {Apart from the ribosome, the crystal structure of the bacterial RNase P in complex with a tRNA, reported by Reiter and colleagues recently, constitutes the first example of a multiple turnover RNA enzyme. Except in rare exceptions, RNase P is ubiquitous and, like the ribosome, is older than the initial branch point of the phylogenetic tree. Importantly, the structure shows how the RNA and the protein moieties cooperate to process the pre-tRNA substrates. The catalytic site comprises some critical RNA residues spread over the secondary structure but gathered in a compact volume next to the protein, which helps recognize and orient the substrate. The discussion here outlines some important aspects of that crystal structure, some of which could apply to RNA molecules in general.},
keywords = {RNase P Multiple-turnover ribozyme RNARNA interactions Molecular evolution Crystallography, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Apart from the ribosome, the crystal structure of the bacterial RNase P in complex with a tRNA, reported by Reiter and colleagues recently, constitutes the first example of a multiple turnover RNA enzyme. Except in rare exceptions, RNase P is ubiquitous and, like the ribosome, is older than the initial branch point of the phylogenetic tree. Importantly, the structure shows how the RNA and the protein moieties cooperate to process the pre-tRNA substrates. The catalytic site comprises some critical RNA residues spread over the secondary structure but gathered in a compact volume next to the protein, which helps recognize and orient the substrate. The discussion here outlines some important aspects of that crystal structure, some of which could apply to RNA molecules in general.
2010
Giuliodori A M, Pietro F Di, Marzi S, Masquida B, Wagner R, Romby P, Gualerzi C O, Pon C L
The cspA mRNA is a thermosensor that modulates translation of the cold-shock protein CspA Journal Article
In: Mol Cell, vol. 37, no. 1, pp. 21-33, 2010, ISBN: 20129052, (1097-4164 (Electronic) 1097-2765 (Linking) Journal Article Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: 5' Untranslated Regions Acclimatization *Cold Temperature Escherichia coli/*genetics/metabolism Escherichia coli Proteins/genetics/*physiology Gene Expression Regulation, Bacterial Heat-Shock Proteins/genetics/*physiology Models, Genetic Nucleic Acid Conformation *Protein Biosynthesis RNA, Messenger/chemistry/*physiology, ROMBY, Unité ARN, WESTHOF
@article{,
title = {The cspA mRNA is a thermosensor that modulates translation of the cold-shock protein CspA},
author = {A M Giuliodori and F Di Pietro and S Marzi and B Masquida and R Wagner and P Romby and C O Gualerzi and C L Pon},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20129052},
isbn = {20129052},
year = {2010},
date = {2010-01-01},
journal = {Mol Cell},
volume = {37},
number = {1},
pages = {21-33},
abstract = {Cold induction of cspA, the paradigm Escherichia coli cold-shock gene, is mainly subject to posttranscriptional control, partly promoted by cis-acting elements of its transcript, whose secondary structure at 37 degrees C and at cold-shock temperature has been elucidated here by enzymatic and chemical probing. The structures, which were also validated by mutagenesis, demonstrate that cspA mRNA undergoes a temperature-dependent structural rearrangement, likely resulting from stabilization in the cold of an otherwise thermodynamically unstable folding intermediate. At low temperature, the "cold-shock" structure is more efficiently translated and somewhat less susceptible to degradation than the 37 degrees C structure. Overall, our data shed light on a molecular mechanism at the basis of the cold-shock response, indicating that cspA mRNA is able to sense temperature downshifts, adopting functionally distinct structures at different temperatures, even without the aid of trans-acting factors. Unlike with other previously studied RNA thermometers, these structural rearrangements do not result from melting of hairpin structures.},
note = {1097-4164 (Electronic)
1097-2765 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {5' Untranslated Regions Acclimatization *Cold Temperature Escherichia coli/*genetics/metabolism Escherichia coli Proteins/genetics/*physiology Gene Expression Regulation, Bacterial Heat-Shock Proteins/genetics/*physiology Models, Genetic Nucleic Acid Conformation *Protein Biosynthesis RNA, Messenger/chemistry/*physiology, ROMBY, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Cold induction of cspA, the paradigm Escherichia coli cold-shock gene, is mainly subject to posttranscriptional control, partly promoted by cis-acting elements of its transcript, whose secondary structure at 37 degrees C and at cold-shock temperature has been elucidated here by enzymatic and chemical probing. The structures, which were also validated by mutagenesis, demonstrate that cspA mRNA undergoes a temperature-dependent structural rearrangement, likely resulting from stabilization in the cold of an otherwise thermodynamically unstable folding intermediate. At low temperature, the "cold-shock" structure is more efficiently translated and somewhat less susceptible to degradation than the 37 degrees C structure. Overall, our data shed light on a molecular mechanism at the basis of the cold-shock response, indicating that cspA mRNA is able to sense temperature downshifts, adopting functionally distinct structures at different temperatures, even without the aid of trans-acting factors. Unlike with other previously studied RNA thermometers, these structural rearrangements do not result from melting of hairpin structures.
2009
Kondo J.
[Exploring the "motion" = "function" of the ribosomal A-site molecular switch] Journal Article
In: Tanpakushitsu Kakusan Koso, vol. 54, no. 11, pp. 1356-62, 2009, (0039-9450 (Print) 0039-9450 (Linking) Journal Article Review).
BibTeX | Tags: *Binding, *RNA/genetics, Agents/adverse, Anti-Bacterial, Bacteria/drug, Biosynthesis/genetics, Crystallography, Disorders/genetics, effects, effects/pharmacology, Hearing, Humans, Mutation, Protein, Ribosomes/chemistry/*genetics/*physiology, RNA, Sites, Transfer, Untranslated, WESTHOF, X-Ray
@article{,
title = {[Exploring the "motion" = "function" of the ribosomal A-site molecular switch]},
author = { J. Kondo},
year = {2009},
date = {2009-01-01},
journal = {Tanpakushitsu Kakusan Koso},
volume = {54},
number = {11},
pages = {1356-62},
note = {0039-9450 (Print)
0039-9450 (Linking)
Journal Article
Review},
keywords = {*Binding, *RNA/genetics, Agents/adverse, Anti-Bacterial, Bacteria/drug, Biosynthesis/genetics, Crystallography, Disorders/genetics, effects, effects/pharmacology, Hearing, Humans, Mutation, Protein, Ribosomes/chemistry/*genetics/*physiology, RNA, Sites, Transfer, Untranslated, WESTHOF, X-Ray},
pubstate = {published},
tppubtype = {article}
}
Michel F, Costa M, Westhof E
The ribozyme core of group II introns: a structure in want of partners Journal Article
In: Trends Biochem Sci, vol. 34, no. 4, pp. 189-199, 2009, ISBN: 19299141, (0968-0004 (Print) Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {The ribozyme core of group II introns: a structure in want of partners},
author = {F Michel and M Costa and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19299141},
isbn = {19299141},
year = {2009},
date = {2009-01-01},
journal = {Trends Biochem Sci},
volume = {34},
number = {4},
pages = {189-199},
abstract = {Group II introns contain a large ribozyme, which catalyzes self-splicing, and the coding sequence of a reverse transcriptase, the function of which is to cooperate with the ribozyme to achieve genomic mobility. Despite its lack of substrates for both steps of the splicing process, the crystal structure of a group II ribozyme reveals the location of two metal ions most likely to be involved in catalysis; the RNA structure that binds to these ions results from the bending of a local motif by the folding of the rest of the ribozyme. The stage is now set to determine where the intron-encoded protein binds to its partner and whether the spliceosome uses a counterpart of the group II catalytic center to excise nuclear pre-messenger introns.},
note = {0968-0004 (Print)
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Group II introns contain a large ribozyme, which catalyzes self-splicing, and the coding sequence of a reverse transcriptase, the function of which is to cooperate with the ribozyme to achieve genomic mobility. Despite its lack of substrates for both steps of the splicing process, the crystal structure of a group II ribozyme reveals the location of two metal ions most likely to be involved in catalysis; the RNA structure that binds to these ions results from the bending of a local motif by the folding of the rest of the ribozyme. The stage is now set to determine where the intron-encoded protein binds to its partner and whether the spliceosome uses a counterpart of the group II catalytic center to excise nuclear pre-messenger introns.
Hashem Y, Auffinger P
A short guide for molecular dynamics simulations of RNA systems Journal Article
In: Methods, vol. 47, no. 3, pp. 187-197, 2009, ISBN: 18930152, (1095-9130 (Electronic) Journal Article Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {A short guide for molecular dynamics simulations of RNA systems},
author = {Y Hashem and P Auffinger},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18930152},
isbn = {18930152},
year = {2009},
date = {2009-01-01},
journal = {Methods},
volume = {47},
number = {3},
pages = {187-197},
abstract = {As a result of important methodological advances and of the rapid growth of experimental data, the number of molecular dynamics (MD) simulations related to RNA systems has significantly increased. However, such MD simulations are not straightforward and great care has to be exerted during the setup stage in order to choose the appropriate MD package, force fields and ionic conditions. Furthermore, the choice and a correct evaluation of the main characteristics of the starting structure are primordial for the generation of informative and reliable MD trajectories since experimental structures are not void of inaccuracies and errors. The aim of this review is to provide, through numerous examples, practical guidelines for the setup of MD simulations, the choice of ionic conditions and the detection and correction of experimental inaccuracies in order to start MD simulations of nucleic acid systems under the best auspices.},
note = {1095-9130 (Electronic)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
As a result of important methodological advances and of the rapid growth of experimental data, the number of molecular dynamics (MD) simulations related to RNA systems has significantly increased. However, such MD simulations are not straightforward and great care has to be exerted during the setup stage in order to choose the appropriate MD package, force fields and ionic conditions. Furthermore, the choice and a correct evaluation of the main characteristics of the starting structure are primordial for the generation of informative and reliable MD trajectories since experimental structures are not void of inaccuracies and errors. The aim of this review is to provide, through numerous examples, practical guidelines for the setup of MD simulations, the choice of ionic conditions and the detection and correction of experimental inaccuracies in order to start MD simulations of nucleic acid systems under the best auspices.
Hammann C, Westhof E
The unforeseeable hammerhead ribozyme Journal Article
In: F1000 Biol Rep, vol. 1, pp. 6, 2009, ISSN: 1757-594X (Electronic) 1757-594X (Linking), (Hammann, Christian Westhof, Eric England F1000 biology reports F1000 Biol Rep. 2009 Jan 21;1. pii: 6.).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {The unforeseeable hammerhead ribozyme},
author = {C Hammann and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20948624},
doi = {10.3410/B1-6},
issn = {1757-594X (Electronic)
1757-594X (Linking)},
year = {2009},
date = {2009-01-01},
journal = {F1000 Biol Rep},
volume = {1},
pages = {6},
abstract = {Despite its small size, the complex behavior of the hammerhead ribozyme keeps surprising us, even more than 20 years after its discovery. Here, we summarize recent developments in the field, in particular the discovery of the first split hammerhead ribozyme.},
note = {Hammann, Christian
Westhof, Eric
England
F1000 biology reports
F1000 Biol Rep. 2009 Jan 21;1. pii: 6.},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Despite its small size, the complex behavior of the hammerhead ribozyme keeps surprising us, even more than 20 years after its discovery. Here, we summarize recent developments in the field, in particular the discovery of the first split hammerhead ribozyme.
Fritsch V, Westhof E
Structure des nucléotides et des acides nucléiques Book Chapter
In: Weil, J H (Ed.): Biochemie Générale 11e Edition, pp. 619-624, Dunod, Paris, 2009.
Links | BibTeX | Tags: Unité ARN, WESTHOF
@inbook{,
title = {Structure des nucléotides et des acides nucléiques},
author = {V Fritsch and E Westhof},
editor = {J H Weil},
url = {http://www.unitheque.com/Livre/dunod/Sciences_sup/Biochimie_generale-31587.html},
year = {2009},
date = {2009-01-01},
booktitle = {Biochemie Générale 11e Edition},
pages = {619-624},
publisher = {Dunod},
address = {Paris},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {inbook}
}
Fritsch V, Westhof E
Molecular adaptation in RNA complexes Journal Article
In: Structure, vol. 17, no. 6, pp. 784-786, 2009, ISBN: 19523895, (1878-4186 (Electronic) Journal Article).
Abstract | Links | BibTeX | Tags: Unité ARN, WESTHOF
@article{,
title = {Molecular adaptation in RNA complexes},
author = {V Fritsch and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19523895},
isbn = {19523895},
year = {2009},
date = {2009-01-01},
journal = {Structure},
volume = {17},
number = {6},
pages = {784-786},
abstract = {In this issue, Batey and colleagues show that the purine riboswitch is able to bind purine analogs by exploiting various strategies, including lateral shifts of the bases and, most importantly, changes in ligand tautomeric form.},
note = {1878-4186 (Electronic)
Journal Article},
keywords = {Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
In this issue, Batey and colleagues show that the purine riboswitch is able to bind purine analogs by exploiting various strategies, including lateral shifts of the bases and, most importantly, changes in ligand tautomeric form.
Kondo J
[Exploring the Journal Article
In: Tanpakushitsu Kakusan Koso, vol. 54, no. 11, pp. 1356-1362, 2009, ISBN: 19764470, (0039-9450 (Print) 0039-9450 (Linking) Journal Article Review).
Links | BibTeX | Tags: Anti-Bacterial Agents/adverse effects/pharmacology Bacteria/drug effects *Binding Sites Crystallography, Transfer RNA, Unité ARN, Untranslated Ribosomes/chemistry/*genetics/*physiology, WESTHOF, X-Ray Hearing Disorders/genetics Humans Mutation Protein Biosynthesis/genetics *RNA/genetics RNA
@article{,
title = {[Exploring the },
author = {J Kondo},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19764470},
isbn = {19764470},
year = {2009},
date = {2009-01-01},
journal = {Tanpakushitsu Kakusan Koso},
volume = {54},
number = {11},
pages = {1356-1362},
note = {0039-9450 (Print)
0039-9450 (Linking)
Journal Article
Review},
keywords = {Anti-Bacterial Agents/adverse effects/pharmacology Bacteria/drug effects *Binding Sites Crystallography, Transfer RNA, Unité ARN, Untranslated Ribosomes/chemistry/*genetics/*physiology, WESTHOF, X-Ray Hearing Disorders/genetics Humans Mutation Protein Biosynthesis/genetics *RNA/genetics RNA},
pubstate = {published},
tppubtype = {article}
}
Romby P, Marzi S, Westhof E
[The atomic structure of the ribosome into the spotlight] Journal Article
In: Med Sci (Paris), vol. 25, no. 11, pp. 977-981, 2009, ISBN: 19951677, (0767-0974 (Print) 0767-0974 (Linking) Journal Article).
Links | BibTeX | Tags: ROMBY, Unité ARN, WESTHOF
@article{,
title = {[The atomic structure of the ribosome into the spotlight]},
author = {P Romby and S Marzi and E Westhof},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19951677},
isbn = {19951677},
year = {2009},
date = {2009-01-01},
journal = {Med Sci (Paris)},
volume = {25},
number = {11},
pages = {977-981},
note = {0767-0974 (Print)
0767-0974 (Linking)
Journal Article},
keywords = {ROMBY, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Nechooshtan G, Elgrably-Weiss M, Sheaffer A, Westhof E, Altuvia S
A pH-responsive riboregulator Journal Article
In: Genes Dev, vol. 23, no. 22, pp. 2650-2662, 2009, ISBN: 19933154, (1549-5477 (Electronic) 0890-9369 (Linking) Journal Article Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: Bacterial Hydrogen-Ion Concentration Mutation/genetics Nucleic Acid Conformation RNA Precursors/chemistry RNA, Bacterial/chemistry/genetics, Base Pairing Conserved Sequence Escherichia coli/*genetics/*metabolism Escherichia coli Proteins/genetics *Gene Expression Regulation, Unité ARN, WESTHOF
@article{,
title = {A pH-responsive riboregulator},
author = {G Nechooshtan and M Elgrably-Weiss and A Sheaffer and E Westhof and S Altuvia},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19933154},
isbn = {19933154},
year = {2009},
date = {2009-01-01},
journal = {Genes Dev},
volume = {23},
number = {22},
pages = {2650-2662},
abstract = {The locus alx, which encodes a putative transporter, was discovered previously in a screen for genes induced under extreme alkaline conditions. Here we show that the RNA region preceding the alx ORF acts as a pH-responsive element, which, in response to high pH, leads to an increase in alx expression. Under normal growth conditions this RNA region forms a translationally inactive structure, but when exposed to high pH, a translationally active structure is formed to produce Alx. Formation of the active structure occurs while transcription is in progress under alkaline conditions and involves pausing of RNA polymerase at two distinct sites. Alkali increases the longevity of pausing at these sites and thereby interferes with formation of the inactive structure and promotes folding of the active one. The alx locus represents the first example of a pH-responsive riboregulator of gene expression, introducing a novel regulatory mechanism that involves RNA folding dynamics driven by pH.},
note = {1549-5477 (Electronic)
0890-9369 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {Bacterial Hydrogen-Ion Concentration Mutation/genetics Nucleic Acid Conformation RNA Precursors/chemistry RNA, Bacterial/chemistry/genetics, Base Pairing Conserved Sequence Escherichia coli/*genetics/*metabolism Escherichia coli Proteins/genetics *Gene Expression Regulation, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
The locus alx, which encodes a putative transporter, was discovered previously in a screen for genes induced under extreme alkaline conditions. Here we show that the RNA region preceding the alx ORF acts as a pH-responsive element, which, in response to high pH, leads to an increase in alx expression. Under normal growth conditions this RNA region forms a translationally inactive structure, but when exposed to high pH, a translationally active structure is formed to produce Alx. Formation of the active structure occurs while transcription is in progress under alkaline conditions and involves pausing of RNA polymerase at two distinct sites. Alkali increases the longevity of pausing at these sites and thereby interferes with formation of the inactive structure and promotes folding of the active one. The alx locus represents the first example of a pH-responsive riboregulator of gene expression, introducing a novel regulatory mechanism that involves RNA folding dynamics driven by pH.
Souciet J L, Dujon B, Gaillardin C, Johnston M, Baret P V, Cliften P, Sherman D J, Weissenbach J, Westhof E, Wincker P, Jubin C, Poulain J, Barbe V, Segurens B, Artiguenave F, Anthouard V, Vacherie B, Val M E, Fulton R S, Minx P, Wilson R, Durrens P, Jean G, Marck C, Martin T, Nikolski M, Rolland T, Seret M L, Casaregola S, Despons L, Fairhead C, Fischer G, Lafontaine I, Leh V, Lemaire M, de Montigny J, Neuveglise C, Thierry A, Blanc-Lenfle I, Bleykasten C, Diffels J, Fritsch E, Frangeul L, Goeffon A, Jauniaux N, Kachouri-Lafond R, Payen C, Potier S, Pribylova L, Ozanne C, Richard G F, Sacerdot C, Straub M L, Talla E
Comparative genomics of protoploid Saccharomycetaceae Journal Article
In: Genome Res, vol. 19, no. 10, pp. 1696-1709, 2009, ISBN: 19525356, (1549-5469 (Electronic) 1088-9051 (Linking) Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: DNA Transposable Elements/genetics/physiology Eremothecium/genetics Gene Duplication Genes, Fungal Genomics/*methods Inteins/genetics Kluyveromyces/genetics Molecular Sequence Data Open Reading Frames/genetics Phylogeny RNA, Fungal/genetics *Genome, Unité ARN, Untranslated/genetics Saccharomyces/genetics Saccharomycetales/*genetics Spliceosomes/metabolism Zygosaccharomyces/genetics, WESTHOF
@article{,
title = {Comparative genomics of protoploid Saccharomycetaceae},
author = {J L Souciet and B Dujon and C Gaillardin and M Johnston and P V Baret and P Cliften and D J Sherman and J Weissenbach and E Westhof and P Wincker and C Jubin and J Poulain and V Barbe and B Segurens and F Artiguenave and V Anthouard and B Vacherie and M E Val and R S Fulton and P Minx and R Wilson and P Durrens and G Jean and C Marck and T Martin and M Nikolski and T Rolland and M L Seret and S Casaregola and L Despons and C Fairhead and G Fischer and I Lafontaine and V Leh and M Lemaire and J de Montigny and C Neuveglise and A Thierry and I Blanc-Lenfle and C Bleykasten and J Diffels and E Fritsch and L Frangeul and A Goeffon and N Jauniaux and R Kachouri-Lafond and C Payen and S Potier and L Pribylova and C Ozanne and G F Richard and C Sacerdot and M L Straub and E Talla},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19525356},
isbn = {19525356},
year = {2009},
date = {2009-01-01},
journal = {Genome Res},
volume = {19},
number = {10},
pages = {1696-1709},
abstract = {Our knowledge of yeast genomes remains largely dominated by the extensive studies on Saccharomyces cerevisiae and the consequences of its ancestral duplication, leaving the evolution of the entire class of hemiascomycetes only partly explored. We concentrate here on five species of Saccharomycetaceae, a large subdivision of hemiascomycetes, that we call "protoploid" because they diverged from the S. cerevisiae lineage prior to its genome duplication. We determined the complete genome sequences of three of these species: Kluyveromyces (Lachancea) thermotolerans and Saccharomyces (Lachancea) kluyveri (two members of the newly described Lachancea clade), and Zygosaccharomyces rouxii. We included in our comparisons the previously available sequences of Kluyveromyces lactis and Ashbya (Eremothecium) gossypii. Despite their broad evolutionary range and significant individual variations in each lineage, the five protoploid Saccharomycetaceae share a core repertoire of approximately 3300 protein families and a high degree of conserved synteny. Synteny blocks were used to define gene orthology and to infer ancestors. Far from representing minimal genomes without redundancy, the five protoploid yeasts contain numerous copies of paralogous genes, either dispersed or in tandem arrays, that, altogether, constitute a third of each genome. Ancient, conserved paralogs as well as novel, lineage-specific paralogs were identified.},
note = {1549-5469 (Electronic)
1088-9051 (Linking)
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't},
keywords = {DNA Transposable Elements/genetics/physiology Eremothecium/genetics Gene Duplication Genes, Fungal Genomics/*methods Inteins/genetics Kluyveromyces/genetics Molecular Sequence Data Open Reading Frames/genetics Phylogeny RNA, Fungal/genetics *Genome, Unité ARN, Untranslated/genetics Saccharomyces/genetics Saccharomycetales/*genetics Spliceosomes/metabolism Zygosaccharomyces/genetics, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Our knowledge of yeast genomes remains largely dominated by the extensive studies on Saccharomyces cerevisiae and the consequences of its ancestral duplication, leaving the evolution of the entire class of hemiascomycetes only partly explored. We concentrate here on five species of Saccharomycetaceae, a large subdivision of hemiascomycetes, that we call "protoploid" because they diverged from the S. cerevisiae lineage prior to its genome duplication. We determined the complete genome sequences of three of these species: Kluyveromyces (Lachancea) thermotolerans and Saccharomyces (Lachancea) kluyveri (two members of the newly described Lachancea clade), and Zygosaccharomyces rouxii. We included in our comparisons the previously available sequences of Kluyveromyces lactis and Ashbya (Eremothecium) gossypii. Despite their broad evolutionary range and significant individual variations in each lineage, the five protoploid Saccharomycetaceae share a core repertoire of approximately 3300 protein families and a high degree of conserved synteny. Synteny blocks were used to define gene orthology and to infer ancestors. Far from representing minimal genomes without redundancy, the five protoploid yeasts contain numerous copies of paralogous genes, either dispersed or in tandem arrays, that, altogether, constitute a third of each genome. Ancient, conserved paralogs as well as novel, lineage-specific paralogs were identified.
Stombaugh J, Zirbel C L, Westhof E, Leontis N B
Frequency and isostericity of RNA base pairs Journal Article
In: Nucleic Acids Res, vol. 37, no. 7, pp. 2294-2312, 2009, ISBN: 19240142, (1362-4962 (Electronic) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.).
Abstract | Links | BibTeX | Tags: ase Pairing Base Sequence Models, Bacterial/chemistry RNA, Molecular Nucleic Acid Conformation RNA/*chemistry RNA, Ribosomal/chemistry Sequence Alignment Sequence Analysis, RNA, Unité ARN, WESTHOF
@article{,
title = {Frequency and isostericity of RNA base pairs},
author = {J Stombaugh and C L Zirbel and E Westhof and N B Leontis},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19240142},
isbn = {19240142},
year = {2009},
date = {2009-01-01},
journal = {Nucleic Acids Res},
volume = {37},
number = {7},
pages = {2294-2312},
abstract = {Most of the hairpin, internal and junction loops that appear single-stranded in standard RNA secondary structures form recurrent 3D motifs, where non-Watson-Crick base pairs play a central role. Non-Watson-Crick base pairs also play crucial roles in tertiary contacts in structured RNA molecules. We previously classified RNA base pairs geometrically so as to group together those base pairs that are structurally similar (isosteric) and therefore able to substitute for each other by mutation without disrupting the 3D structure. Here, we introduce a quantitative measure of base pair isostericity, the IsoDiscrepancy Index (IDI), to more accurately determine which base pair substitutions can potentially occur in conserved motifs. We extract and classify base pairs from a reduced-redundancy set of RNA 3D structures from the Protein Data Bank (PDB) and calculate centroids (exemplars) for each base combination and geometric base pair type (family). We use the exemplars and IDI values to update our online Basepair Catalog and the Isostericity Matrices (IM) for each base pair family. From the database of base pairs observed in 3D structures we derive base pair occurrence frequencies for each of the 12 geometric base pair families. In order to improve the statistics from the 3D structures, we also derive base pair occurrence frequencies from rRNA sequence alignments.},
note = {1362-4962 (Electronic)
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.},
keywords = {ase Pairing Base Sequence Models, Bacterial/chemistry RNA, Molecular Nucleic Acid Conformation RNA/*chemistry RNA, Ribosomal/chemistry Sequence Alignment Sequence Analysis, RNA, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Most of the hairpin, internal and junction loops that appear single-stranded in standard RNA secondary structures form recurrent 3D motifs, where non-Watson-Crick base pairs play a central role. Non-Watson-Crick base pairs also play crucial roles in tertiary contacts in structured RNA molecules. We previously classified RNA base pairs geometrically so as to group together those base pairs that are structurally similar (isosteric) and therefore able to substitute for each other by mutation without disrupting the 3D structure. Here, we introduce a quantitative measure of base pair isostericity, the IsoDiscrepancy Index (IDI), to more accurately determine which base pair substitutions can potentially occur in conserved motifs. We extract and classify base pairs from a reduced-redundancy set of RNA 3D structures from the Protein Data Bank (PDB) and calculate centroids (exemplars) for each base combination and geometric base pair type (family). We use the exemplars and IDI values to update our online Basepair Catalog and the Isostericity Matrices (IM) for each base pair family. From the database of base pairs observed in 3D structures we derive base pair occurrence frequencies for each of the 12 geometric base pair families. In order to improve the statistics from the 3D structures, we also derive base pair occurrence frequencies from rRNA sequence alignments.
Kachouri-Lafond R, Dujon B, Gilson E, Westhof E, Fairhead C, Teixeira M T
Large telomerase RNA, telomere length heterogeneity and escape from senescence in Candida glabrata Journal Article
In: FEBS Lett, vol. 583, no. 22, pp. 3605-3610, 2009, ISBN: 19840797, (1873-3468 (Electronic) 0014-5793 (Linking) Journal Article Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: Base Sequence Blotting, Fungal/chemistry/*genetics Sequence Homology, Fungal/genetics Flow Cytometry Gene Deletion Molecular Sequence Data Mutation Nucleic Acid Conformation RNA/chemistry/*genetics RNA, Nucleic Acid Telomerase/chemistry/*genetics Telomere/*genetics, Southern Candida glabrata/enzymology/*genetics/growth & development Cell Division DNA, Unité ARN, WESTHOF
@article{,
title = {Large telomerase RNA, telomere length heterogeneity and escape from senescence in Candida glabrata},
author = {R Kachouri-Lafond and B Dujon and E Gilson and E Westhof and C Fairhead and M T Teixeira},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19840797},
isbn = {19840797},
year = {2009},
date = {2009-01-01},
journal = {FEBS Lett},
volume = {583},
number = {22},
pages = {3605-3610},
abstract = {Telomerase, the key enzyme essential for the maintenance of eukaryotic chromosome ends, contains a reverse transcriptase and an RNA that provides the template for the synthesis of telomeric repeats. Here, we characterize the telomerase subunits in the hemiascomycete yeast Candida glabrata. We propose a secondary structure model for the telomerase RNA that is the largest described to date. Telomerase deletion mutants show a progressive shortening of telomeres and a modest loss of viability. Frequent post-senescence survivors emerge that possess long telomeric repeat tracts. We suggest that the high telomere length heterogeneity accounts for this distinct senescence phenotype.},
note = {1873-3468 (Electronic)
0014-5793 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {Base Sequence Blotting, Fungal/chemistry/*genetics Sequence Homology, Fungal/genetics Flow Cytometry Gene Deletion Molecular Sequence Data Mutation Nucleic Acid Conformation RNA/chemistry/*genetics RNA, Nucleic Acid Telomerase/chemistry/*genetics Telomere/*genetics, Southern Candida glabrata/enzymology/*genetics/growth & development Cell Division DNA, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
Telomerase, the key enzyme essential for the maintenance of eukaryotic chromosome ends, contains a reverse transcriptase and an RNA that provides the template for the synthesis of telomeric repeats. Here, we characterize the telomerase subunits in the hemiascomycete yeast Candida glabrata. We propose a secondary structure model for the telomerase RNA that is the largest described to date. Telomerase deletion mutants show a progressive shortening of telomeres and a modest loss of viability. Frequent post-senescence survivors emerge that possess long telomeric repeat tracts. We suggest that the high telomere length heterogeneity accounts for this distinct senescence phenotype.
Parisien M, Cruz J A, Westhof E, Major F
New metrics for comparing and assessing discrepancies between RNA 3D structures and models Journal Article
In: RNA, vol. 15, no. 10, pp. 1875-1885, 2009, ISBN: 19710185, (1469-9001 (Electronic) 1355-8382 (Linking) Comparative Study Journal Article Research Support, Non-U.S. Gov't).
Abstract | Links | BibTeX | Tags: 28S/*chemistry Rats, Animals Base Pairing Calibration *Models, Molecular *Nucleic Acid Conformation RNA, Ribosomal, Unité ARN, WESTHOF
@article{,
title = {New metrics for comparing and assessing discrepancies between RNA 3D structures and models},
author = {M Parisien and J A Cruz and E Westhof and F Major},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19710185},
isbn = {19710185},
year = {2009},
date = {2009-01-01},
journal = {RNA},
volume = {15},
number = {10},
pages = {1875-1885},
abstract = {To benchmark progress made in RNA three-dimensional modeling and assess newly developed techniques, reliable and meaningful comparison metrics and associated tools are necessary. Generally, the average root-mean-square deviations (RMSDs) are quoted. However, RMSD can be misleading since errors are spread over the whole molecule and do not account for the specificity of RNA base interactions. Here, we introduce two new metrics that are particularly suitable to RNAs: the deformation index and deformation profile. The deformation index is calibrated by the interaction network fidelity, which considers base-base-stacking and base-base-pairing interactions within the target structure. The deformation profile highlights dissimilarities between structures at the nucleotide scale for both intradomain and interdomain interactions. Our results show that there is little correlation between RMSD and interaction network fidelity. The deformation profile is a tool that allows for rapid assessment of the origins of discrepancies.},
note = {1469-9001 (Electronic)
1355-8382 (Linking)
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {28S/*chemistry Rats, Animals Base Pairing Calibration *Models, Molecular *Nucleic Acid Conformation RNA, Ribosomal, Unité ARN, WESTHOF},
pubstate = {published},
tppubtype = {article}
}
To benchmark progress made in RNA three-dimensional modeling and assess newly developed techniques, reliable and meaningful comparison metrics and associated tools are necessary. Generally, the average root-mean-square deviations (RMSDs) are quoted. However, RMSD can be misleading since errors are spread over the whole molecule and do not account for the specificity of RNA base interactions. Here, we introduce two new metrics that are particularly suitable to RNAs: the deformation index and deformation profile. The deformation index is calibrated by the interaction network fidelity, which considers base-base-stacking and base-base-pairing interactions within the target structure. The deformation profile highlights dissimilarities between structures at the nucleotide scale for both intradomain and interdomain interactions. Our results show that there is little correlation between RMSD and interaction network fidelity. The deformation profile is a tool that allows for rapid assessment of the origins of discrepancies.
Westhof E, Patel D J
Nucleic acids: how high resolution structural biology help us to understand Darwinian evolution Journal Article
In: Curr Opin Struct Biol, vol. 19, no. 3, pp. 235-238, 2009, ISBN: 19482468, (1879-033X (Electronic) Editorial Introductory Journal Article).
Links | BibTeX | Tags: *Evolution, Molecular Humans Molecular Biology/*methods Nucleic Acids/*chemistry/metabolism Periodicals as Topic, Unité ARN, WESTHOF