Publications
2023
Ponce José R Jaramillo, Frugier Magali
Plasmodium, the Apicomplexa Outlier When It Comes to Protein Synthesis Article de journal
Dans: Biomolecules, vol. 14, no. 1, p. 46, 2023, ISSN: 2218-273X.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{pmid38254646,
title = {Plasmodium, the Apicomplexa Outlier When It Comes to Protein Synthesis},
author = {José R Jaramillo Ponce and Magali Frugier},
doi = {10.3390/biom14010046},
issn = {2218-273X},
year = {2023},
date = {2023-12-01},
urldate = {2023-12-01},
journal = {Biomolecules},
volume = {14},
number = {1},
pages = {46},
abstract = {Plasmodium is an obligate intracellular parasite that has numerous interactions with different hosts during its elaborate life cycle. This is also the case for the other parasites belonging to the same phylum Apicomplexa. In this study, we bioinformatically identified the components of the multi-synthetase complexes (MSCs) of several Apicomplexa parasites and modelled their assembly using AlphaFold2. It appears that none of these MSCs resemble the two MSCs that we have identified and characterized in Plasmodium. Indeed, tRip, the central protein involved in the association of the two Plasmodium MSCs is different from its homologues, suggesting also that the tRip-dependent import of exogenous tRNAs is not conserved in other apicomplexan parasites. Based on this observation, we searched for obvious differences that could explain the singularity of Plasmodium protein synthesis by comparing tRNA genes and amino acid usage in the different genomes. We noted a contradiction between the large number of asparagine residues used in Plasmodium proteomes and the single gene encoding the tRNA that inserts them into proteins. This observation remains true for all the Plasmodia strains studied, even those that do not contain long asparagine homorepeats. },
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Pitolli Martina, Cela Marta, Paulus Caroline, Rudinger-Thirion Joëlle, Frugier Magali
RNA aptamers developed against tRip: A preliminary approach targeting tRNA entry in Plasmodium Article de journal
Dans: Biochimie, vol. 217, p. 106-115, 2023, ISSN: 1638-6183.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{pmid37414209,
title = {RNA aptamers developed against tRip: A preliminary approach targeting tRNA entry in Plasmodium},
author = {Martina Pitolli and Marta Cela and Caroline Paulus and Joëlle Rudinger-Thirion and Magali Frugier},
doi = {10.1016/j.biochi.2023.06.011},
issn = {1638-6183},
year = {2023},
date = {2023-07-01},
urldate = {2023-07-01},
journal = {Biochimie},
volume = {217},
pages = {106-115},
abstract = {Malaria is caused by Plasmodium parasites that multiply inside host cells and can be lethal when P. falciparum is involved. We identified tRip as a membrane protein that facilitates the import of exogenous transfer RNA (tRNA) into the parasite. tRip encompasses a tRNA binding domain exposed on the parasite surface. We used the SELEX approach to isolate high-affinity and specific tRip-binding RNA motifs from a library of random 25 nucleotide-long sequences. In five rounds of combined negative and positive selections, an enriched pool of aptamers was obtained; sequencing revealed that they were all different in their primary sequence; only by comparing their structure predictions did most of the selected aptamers reveal a conserved 5-nucleotide motif sequence. We showed that the integral motif is essential for tRip-binding while the rest of the molecule can be significantly reduced or mutated as long as the motif is presented in a single-stranded region. Such RNA aptamers bind in place of the original tRNA substrate and act as an efficient competitor, suggesting that they can block tRip function and slow parasite development.},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Ponce José R Jaramillo, Théobald-Dietrich Anne, Bénas Philippe, Paulus Caroline, Sauter Claude, Frugier Magali
Solution x-ray scattering highlights discrepancies in Plasmodium multi-aminoacyl-tRNA synthetase complexes Article de journal
Dans: Protein Sci, p. e4564, 2023, ISSN: 1469-896X.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, SAUTER, Unité ARN
@article{pmid36606712,
title = {Solution x-ray scattering highlights discrepancies in Plasmodium multi-aminoacyl-tRNA synthetase complexes},
author = {José R Jaramillo Ponce and Anne Théobald-Dietrich and Philippe Bénas and Caroline Paulus and Claude Sauter and Magali Frugier},
doi = {10.1002/pro.4564},
issn = {1469-896X},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Protein Sci},
pages = {e4564},
abstract = {tRip is a tRNA import protein specific to Plasmodium, the causative agent of malaria. In addition to its membrane localization and tRNA trafficking properties, tRip has the capacity to associate with three aminoacyl-tRNA synthetases (aaRS), the glutamyl- (ERS), glutaminyl- (QRS), and methionyl- (MRS) tRNA synthetases. In eukaryotes, such multi-aaRSs complexes (MSC) regulate the moonlighting activities of aaRSs. In Plasmodium, tRip and the three aaRSs all contain an N-terminal GST-like domain involved in the assembly of two independent complexes: the Q-complex (tRip:ERS:QRS) and the M-complex (tRip:ERS:MRS) with a 2:2:2 stoichiometry and in which the association of the GST-like domains of tRip and ERS (tRip-N:ERS-N) is central. In this study, the crystal structure of the N-terminal GST-like domain of ERS was solved and made possible further investigation of the solution architecture of the Q- and M-complexes by small-angle X-ray scattering (SAXS). This strategy relied on the engineering of a tRip-N-ERS-N chimeric protein to study the structural scaffold of both Plasmodium MSCs and confirm the unique homodimerization pattern of tRip in solution. The biological impact of these structural arrangements is discussed. This article is protected by copyright. All rights reserved.},
keywords = {FRUGIER, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2022
Neyroud Anne Sophie, Rudinger-Thirion Joëlle, Frugier Magali, Riley Lisa G, Bidet Maud, Akloul Linda, Simpson Andrea, Gilot David, Christodoulou John, Ravel Célia, Sinclair Andrew H, Belaud-Rotureau Marc-Antoine, Tucker Elena J, Jaillard Sylvie
LARS2 variants can present as premature ovarian insufficiency in the absence of overt hearing loss Article de journal
Dans: Eur J Hum Genet, vol. 31, iss. 4, p. 453-460, 2022, ISSN: 1476-5438.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{pmid36450801,
title = {LARS2 variants can present as premature ovarian insufficiency in the absence of overt hearing loss},
author = {Anne Sophie Neyroud and Joëlle Rudinger-Thirion and Magali Frugier and Lisa G Riley and Maud Bidet and Linda Akloul and Andrea Simpson and David Gilot and John Christodoulou and Célia Ravel and Andrew H Sinclair and Marc-Antoine Belaud-Rotureau and Elena J Tucker and Sylvie Jaillard},
doi = {10.1038/s41431-022-01252-1},
issn = {1476-5438},
year = {2022},
date = {2022-12-01},
urldate = {2022-12-01},
journal = {Eur J Hum Genet},
volume = {31},
issue = {4},
pages = {453-460},
abstract = {Premature ovarian insufficiency (POI) affects 1 in 100 women and is a leading cause of female infertility. There are over 80 genes in which variants can cause POI, with these explaining only a minority of cases. Whole exome sequencing (WES) can be a useful tool for POI patient management, allowing clinical care to be personalized to underlying cause. We performed WES to investigate two French sisters, whose only clinical complaint was POI. Surprisingly, they shared one known and one novel likely pathogenic variant in the Perrault syndrome gene, LARS2. Using amino-acylation studies, we established that the novel missense variant significantly impairs LARS2 function. Perrault syndrome is characterized by sensorineural hearing loss in addition to POI. This molecular diagnosis alerted the sisters to the significance of their difficulty in following conversation. Subsequent audiology assessment revealed a mild bilateral hearing loss. We describe the first cases presenting with perceived isolated POI and causative variants in a Perrault syndrome gene. Our study expands the phenotypic spectrum associated with LARS2 variants and highlights the clinical benefit of having a genetic diagnosis, with prediction of potential co-morbidity and prompt and appropriate medical care, in this case by an audiologist for early detection of hearing loss.},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Chan D. L., Rudinger-Thirion J., Frugier M., Riley L. G., Ho G., Kothur K., Mohammad S. S.
A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders Article de journal
Dans: Brain Dev, vol. 44, no. 2, p. 142-147, 2022, ISBN: 34774383, (1872-7131 (Electronic) 0387-7604 (Linking) Case Reports).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{nokey,
title = {A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders},
author = {D. L. Chan and J. Rudinger-Thirion and M. Frugier and L. G. Riley and G. Ho and K. Kothur and S. S. Mohammad},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=34774383},
doi = {10.1016/j.braindev.2021.10.009},
isbn = {34774383},
year = {2022},
date = {2022-01-01},
journal = {Brain Dev},
volume = {44},
number = {2},
pages = {142-147},
abstract = {INTRODUCTION: Mutations in QARS1, which encodes human glutaminyl-tRNA synthetase, have been associated with epilepsy, developmental regression, progressive microcephaly and cerebral atrophy. Epilepsy caused by variants in QARS1 is usually drug-resistant and intractable. Childhood onset epilepsy is also reported in various aminoacyl-tRNA synthetase disorders. We describe a case with a milder neurological phenotype than previously reported with QARS1 variants and review the seizure associations with aminoacyl-tRNA synthetase disorders. CASE REPORT: The patient is a 4-year-old girl presenting at 6 weeks of age with orofacial dyskinesia and hand stereotypies. She developed focal seizures at 7 months of age. Serial electroencephalograms showed shifting focality. Her seizures were controlled after introduction of carbamazepine. Progress MRI showed very mild cortical volume loss without myelination abnormalities or cerebellar atrophy. She was found to have novel compound heterozygous variants in QARS1 (NM_005051.2): c.[1132C > T];[1574G > A], p.[(Arg378Cys)];[(Arg525Gln)] originally classified as "variants of uncertain significance" and later upgraded to "likely pathogenic" based on functional testing and updated variant database review. Functional testing showed reduced solubility of the corresponding QARS1 mutants in vitro, but only mild two-fold loss in catalytic efficiency with the c.1132C > T variant and no noted change in tRNA(Gln) aminoacylation with the c.1574G > A variant. CONCLUSION: We describe two QARS1 variants associated with overall conserved tRNA aminoacylation activity but characterized by significantly reduced QARS protein solubility, resulting in a milder clinical phenotype. 86% of previous patients reported with QARS1 had epilepsy and 79% were pharmaco-resistant. We also summarise literature regarding epilepsy in aminoacyl-tRNA synthetase disorders, which is also often early onset, severe and drug-refractory.},
note = {1872-7131 (Electronic)
0387-7604 (Linking)
Case Reports},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Ponce J. R. Jaramillo, Kapps D., Paulus C., Chicher J., Frugier M.
Discovery of two distinct aminoacyl-tRNA synthetase complexes anchored to the Plasmodium surface tRNA import protein Article de journal
Dans: J Biol Chem, vol. 298, iss. 6, p. 101987, 2022, ISBN: 35487244, (1083-351X (Electronic) 0021-9258 (Linking) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Labex, PPSE, Unité ARN
@article{nokey,
title = {Discovery of two distinct aminoacyl-tRNA synthetase complexes anchored to the Plasmodium surface tRNA import protein},
author = {J. R. Jaramillo Ponce and D. Kapps and C. Paulus and J. Chicher and M. Frugier},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=35487244},
doi = {0.1016/j.jbc.2022.101987},
isbn = {35487244},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {J Biol Chem},
volume = {298},
issue = {6},
pages = {101987},
abstract = {Aminoacyl-tRNA synthetases (aaRSs) attach amino acids to their cognate transfer RNAs. In eukaryotes, a subset of cytosolic aaRSs is organized into a multi-synthetase complex (MSC), along with specialized scaffolding proteins referred to as aaRS-interacting multifunctional proteins (AIMPs). In Plasmodium, the causative agent of malaria, the tRNA import protein (tRip), is a membrane protein that has been shown to participate in tRNA trafficking; here, we show that tRip also functions as an AIMP. We identified three aaRSs, namely the glutamyl- (ERS), glutaminyl- (QRS), and methionyl- (MRS) tRNA synthetases, which were specifically co-immunoprecipitated with tRip in P. berghei blood stage parasites. All four proteins contain an N-terminal GST-like domain that was demonstrated to be involved in MSC assembly. In contrast to previous studies, further dissection of GST-like interactions identified two exclusive heterotrimeric complexes: the Q-complex (tRip:ERS:QRS) and the M-complex (tRip:ERS:MRS). Gel filtration and light scattering suggest a 2:2:2 stoichiometry for both complexes but with distinct biophysical properties, and mutational analysis further revealed that the GST-like domains of QRS and MRS use different strategies to bind ERS. Taken together our results demonstrate that neither the singular homodimerization of tRip, nor its localization in the parasite plasma membrane prevents the formation of MSCs in Plasmodium. Besides, the extracellular localization of the tRNA-binding module of tRip is compensated by the presence of additional tRNA-binding modules fused to MRS and QRS, providing each MSC with two spatially distinct functions: aminoacylation of intraparasitic tRNAs and binding of extracellular tRNAs. This unique host-pathogen interaction is discussed.},
note = {1083-351X (Electronic)
0021-9258 (Linking)
Journal Article},
keywords = {FRUGIER, Labex, PPSE, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2021
Cela M, Theobald-Dietrich A, Rudinger-Thirion J, Wolff P, Geslain R, Frugier M
Identification of host tRNAs preferentially recognized by the Plasmodium surface protein tRip Article de journal
Dans: Nucleic Acids Res, 2021, ISBN: 34530443, (1362-4962 (Electronic) 0305-1048 (Linking) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: ARN-MS, FRUGIER, Unité ARN
@article{,
title = {Identification of host tRNAs preferentially recognized by the Plasmodium surface protein tRip},
author = {M Cela and A Theobald-Dietrich and J Rudinger-Thirion and P Wolff and R Geslain and M Frugier},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=34530443},
doi = {10.1093/nar/gkab769},
isbn = {34530443},
year = {2021},
date = {2021-01-01},
journal = {Nucleic Acids Res},
abstract = {Malaria is a life-threatening and devastating parasitic disease. Our previous work showed that parasite development requires the import of exogenous transfer RNAs (tRNAs), which represents a novel and unique form of host-pathogen interaction, as well as a potentially druggable target. This import is mediated by tRip (tRNA import protein), a membrane protein located on the parasite surface. tRip displays an extracellular domain homologous to the well-characterized OB-fold tRNA-binding domain, a structural motif known to indiscriminately interact with tRNAs. We used MIST (Microarray Identification of Shifted tRNAs), a previously established in vitro approach, to systematically assess the specificity of complexes between native Homo sapiens tRNAs and recombinant Plasmodium falciparum tRip. We demonstrate that tRip unexpectedly binds to host tRNAs with a wide range of affinities, suggesting that only a small subset of human tRNAs is preferentially imported into the parasite. In particular, we show with in vitro transcribed constructs that tRip does not bind specific tRNAs solely based on their primary sequence, hinting that post-transcriptional modifications modulate the formation of our host/parasite molecular complex. Finally, we discuss the potential utilization of the most efficient tRip ligands for the translation of the parasite's genetic information.},
note = {1362-4962 (Electronic)
0305-1048 (Linking)
Journal Article},
keywords = {ARN-MS, FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Chan D. L., Rudinger-Thirion J., Frugier M., Riley L. G., Ho G., Kothur K., Mohammad S. S.
A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders Article de journal
Dans: Brain Dev, 2021, ISBN: 34774383, (1872-7131 (Electronic) 0387-7604 (Linking) Case Reports).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{nokey,
title = {A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders},
author = {D. L. Chan and J. Rudinger-Thirion and M. Frugier and L. G. Riley and G. Ho and K. Kothur and S. S. Mohammad},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=34774383},
doi = {10.1016/j.braindev.2021.10.009},
isbn = {34774383},
year = {2021},
date = {2021-01-01},
journal = {Brain Dev},
abstract = {INTRODUCTION: Mutations in QARS1, which encodes human glutaminyl-tRNA synthetase, have been associated with epilepsy, developmental regression, progressive microcephaly and cerebral atrophy. Epilepsy caused by variants in QARS1 is usually drug-resistant and intractable. Childhood onset epilepsy is also reported in various aminoacyl-tRNA synthetase disorders. We describe a case with a milder neurological phenotype than previously reported with QARS1 variants and review the seizure associations with aminoacyl-tRNA synthetase disorders. CASE REPORT: The patient is a 4-year-old girl presenting at 6 weeks of age with orofacial dyskinesia and hand stereotypies. She developed focal seizures at 7 months of age. Serial electroencephalograms showed shifting focality. Her seizures were controlled after introduction of carbamazepine. Progress MRI showed very mild cortical volume loss without myelination abnormalities or cerebellar atrophy. She was found to have novel compound heterozygous variants in QARS1 (NM_005051.2): c.[1132C > T];[1574G > A], p.[(Arg378Cys)];[(Arg525Gln)] originally classified as "variants of uncertain significance" and later upgraded to "likely pathogenic" based on functional testing and updated variant database review. Functional testing showed reduced solubility of the corresponding QARS1 mutants in vitro, but only mild two-fold loss in catalytic efficiency with the c.1132C > T variant and no noted change in tRNA(Gln) aminoacylation with the c.1574G > A variant. CONCLUSION: We describe two QARS1 variants associated with overall conserved tRNA aminoacylation activity but characterized by significantly reduced QARS protein solubility, resulting in a milder clinical phenotype. 86% of previous patients reported with QARS1 had epilepsy and 79% were pharmaco-resistant. We also summarise literature regarding epilepsy in aminoacyl-tRNA synthetase disorders, which is also often early onset, severe and drug-refractory.},
note = {1872-7131 (Electronic)
0387-7604 (Linking)
Case Reports},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2020
Théobald-Dietrich A, de Wijn R, Rollet K, Bluhm A, Rudinger-Thirion J, Paulus C, Lorber B, Thureau A, Frugier M, Sauter C
Structural Analysis of RNA by Small-Angle X-ray Scattering Chapitre d'ouvrage
Dans: Arluison, V; Wien, F (Ed.): RNA Spectroscopy: Methods and Protocols, vol. 2113, p. 189-215, Springer Protocols, Humana Press, New York, NY, 2020, ISBN: 32006316.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, IRES Integrative structural biology RNA SEC-SAXS Structure tRNA, SAUTER, Unité ARN
@inbook{,
title = {Structural Analysis of RNA by Small-Angle X-ray Scattering},
author = {A Théobald-Dietrich and R de Wijn and K Rollet and A Bluhm and J Rudinger-Thirion and C Paulus and B Lorber and A Thureau and M Frugier and C Sauter},
editor = {V Arluison and F Wien},
url = {https://pubmed.ncbi.nlm.nih.gov/32006316},
doi = {10.1007/978-1-0716-0278-2_14},
isbn = {32006316},
year = {2020},
date = {2020-01-01},
booktitle = {RNA Spectroscopy: Methods and Protocols},
volume = {2113},
pages = {189-215},
publisher = {Springer Protocols, Humana Press},
address = {New York, NY},
series = {Methods in Molecular Biology},
abstract = {Over the past two decades small-angle X-ray scattering (SAXS) has become a popular method to characterize solutions of biomolecules including ribonucleic acid (RNA). In an integrative structural approach, SAXS is complementary to crystallography, NMR, and electron microscopy and provides information about RNA architecture and dynamics. This chapter highlights the practical advantages of combining size-exclusion chromatography and SAXS at synchrotron facilities. It is illustrated by practical case studies of samples ranging from single hairpins and tRNA to a large IRES. The emphasis is also put on sample preparation which is a critical step of SAXS analysis and on optimized protocols for in vitro RNA synthesis ensuring the production of mg amount of pure and homogeneous molecules.},
keywords = {FRUGIER, IRES Integrative structural biology RNA SEC-SAXS Structure tRNA, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {inbook}
}
Riley L G, Rudinger-Thirion J, Frugier M, Wilson M, Luig M, Alahakoon T I, Nixon C Y, Kirk E P, Roscioli T, Lunke S, Stark Z, Wierenga K J, Palle S, Walsh M, Higgs E, Arbuckle S, Thirukeswaran S, Compton A G, Thorburn D R, Christodoulou J
The Expanding LARS2 Phenotypic Spectrum: HLASA, Perrault Syndrome With Leukodystrophy, and Mitochondrial Myopathy Article de journal
Dans: Hum Mutat, vol. 41, no. 8, p. 1425-1434, 2020, ISBN: 32442335.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Perrault syndrome low frequency hearing loss primary ovarian insufficiency sensorineural hearing loss, Unité ARN
@article{,
title = {The Expanding LARS2 Phenotypic Spectrum: HLASA, Perrault Syndrome With Leukodystrophy, and Mitochondrial Myopathy},
author = {L G Riley and J Rudinger-Thirion and M Frugier and M Wilson and M Luig and T I Alahakoon and C Y Nixon and E P Kirk and T Roscioli and S Lunke and Z Stark and K J Wierenga and S Palle and M Walsh and E Higgs and S Arbuckle and S Thirukeswaran and A G Compton and D R Thorburn and J Christodoulou},
url = {https://pubmed.ncbi.nlm.nih.gov/32442335/?dopt=Abstract},
doi = {doi: 10.1002/humu.24050},
isbn = {32442335},
year = {2020},
date = {2020-01-01},
journal = {Hum Mutat},
volume = {41},
number = {8},
pages = {1425-1434},
abstract = {Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) in both sexes and primary ovarian insufficiency in 46, XX karyotype females. Biallelic variants in five genes are reported to be causative: HSD17B4, HARS2, LARS2, CLPP and C10orf2. Here we present eight families affected by Perrault syndrome. In five families we identified novel or previously reported variants in HSD17B4, LARS2, CLPP and C10orf2. The proband from each family was whole exome sequenced and variants confirmed by Sanger sequencing. A female was compound heterozygous for a known, p.(Gly16Ser) and novel, p.(Val82Phe) variant in D-bifunctional protein (HSD17B4). A family was homozygous for mitochondrial leucyl aminocyl tRNA synthetase (mtLeuRS) (LARS2) p.(Thr522Asn), previously associated with Perrault syndrome. A further family was compound heterozygous for mtLeuRS, p.(Thr522Asn) and a novel variant, p.(Met117Ile). Affected individuals with LARS2 variants had low frequency SNHL, a feature previously described in Perrault syndrome. A female with significant neurological disability was compound heterozygous for p.(Arg323Gln) and p.(Asn399Ser) variants in Twinkle (C10orf2). A male was homozygous for a novel variant in CLPP, p.(Cys144Arg). In three families there were no putative pathogenic variants in these genes confirming additional disease-causing genes remain unidentified. We have expanded the spectrum of disease-causing variants associated with Perrault syndrome.},
keywords = {FRUGIER, Perrault syndrome low frequency hearing loss primary ovarian insufficiency sensorineural hearing loss, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2019
van der Knaap M S, Bugiani M, Mendes M I, Riley L G, Smith D E C, Rudinger-Thirion J, Frugier M, Breur M, Crawford J, van Gaalen J, Schouten M, Willems M, Waisfisz Q, Mau-Them F T, Rodenburg R J, Taft R J, Keren B, Christodoulou J, Depienne C, Simons C, Salomons G S, Mochel F
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy Article de journal
Dans: Neurology, vol. 92, no. 11, p. e1225-e1237, 2019, ISBN: 30737337.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{,
title = {Biallelic variants in \textit{LARS2} and \textit{KARS} cause deafness and (ovario)leukodystrophy},
author = {M S van der Knaap and M Bugiani and M I Mendes and L G Riley and D E C Smith and J Rudinger-Thirion and M Frugier and M Breur and J Crawford and J van Gaalen and M Schouten and M Willems and Q Waisfisz and F T Mau-Them and R J Rodenburg and R J Taft and B Keren and J Christodoulou and C Depienne and C Simons and G S Salomons and F Mochel},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30737337},
doi = {10.1212/WNL.0000000000007098},
isbn = {30737337},
year = {2019},
date = {2019-01-01},
journal = {Neurology},
volume = {92},
number = {11},
pages = {e1225-e1237},
abstract = {OBJECTIVE:
To describe the leukodystrophy caused by pathogenic variants in LARS2 and KARS, encoding mitochondrial leucyl transfer RNA (tRNA) synthase and mitochondrial and cytoplasmic lysyl tRNA synthase, respectively.
METHODS:
We composed a group of 5 patients with leukodystrophy, in whom whole-genome or whole-exome sequencing revealed pathogenic variants in LARS2 or KARS. Clinical information, brain MRIs, and postmortem brain autopsy data were collected. We assessed aminoacylation activities of purified mutant recombinant mitochondrial leucyl tRNA synthase and performed aminoacylation assays on patients' lymphoblasts and fibroblasts.
RESULTS:
Patients had a combination of early-onset deafness and later-onset neurologic deterioration caused by progressive brain white matter abnormalities on MRI. Female patients with LARS2 pathogenic variants had premature ovarian failure. In 2 patients, MRI showed additional signs of early-onset vascular abnormalities. In 2 other patients with LARS2 and KARS pathogenic variants, magnetic resonance spectroscopy revealed elevated white matter lactate, suggesting mitochondrial disease. Pathology in one patient with LARS2 pathogenic variants displayed evidence of primary disease of oligodendrocytes and astrocytes with lack of myelin and deficient astrogliosis. Aminoacylation activities of purified recombinant mutant leucyl tRNA synthase showed a 3-fold loss of catalytic efficiency. Aminoacylation assays on patients' lymphoblasts and fibroblasts showed about 50% reduction of enzyme activity.
CONCLUSION:
This study adds LARS2 and KARS pathogenic variants as gene defects that may underlie deafness, ovarian failure, and leukodystrophy with mitochondrial signature. We discuss the specific MRI characteristics shared by leukodystrophies caused by mitochondrial tRNA synthase defects. We propose to add aminoacylation assays as biochemical diagnostic tools for leukodystrophies.},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
To describe the leukodystrophy caused by pathogenic variants in LARS2 and KARS, encoding mitochondrial leucyl transfer RNA (tRNA) synthase and mitochondrial and cytoplasmic lysyl tRNA synthase, respectively.
METHODS:
We composed a group of 5 patients with leukodystrophy, in whom whole-genome or whole-exome sequencing revealed pathogenic variants in LARS2 or KARS. Clinical information, brain MRIs, and postmortem brain autopsy data were collected. We assessed aminoacylation activities of purified mutant recombinant mitochondrial leucyl tRNA synthase and performed aminoacylation assays on patients' lymphoblasts and fibroblasts.
RESULTS:
Patients had a combination of early-onset deafness and later-onset neurologic deterioration caused by progressive brain white matter abnormalities on MRI. Female patients with LARS2 pathogenic variants had premature ovarian failure. In 2 patients, MRI showed additional signs of early-onset vascular abnormalities. In 2 other patients with LARS2 and KARS pathogenic variants, magnetic resonance spectroscopy revealed elevated white matter lactate, suggesting mitochondrial disease. Pathology in one patient with LARS2 pathogenic variants displayed evidence of primary disease of oligodendrocytes and astrocytes with lack of myelin and deficient astrogliosis. Aminoacylation activities of purified recombinant mutant leucyl tRNA synthase showed a 3-fold loss of catalytic efficiency. Aminoacylation assays on patients' lymphoblasts and fibroblasts showed about 50% reduction of enzyme activity.
CONCLUSION:
This study adds LARS2 and KARS pathogenic variants as gene defects that may underlie deafness, ovarian failure, and leukodystrophy with mitochondrial signature. We discuss the specific MRI characteristics shared by leukodystrophies caused by mitochondrial tRNA synthase defects. We propose to add aminoacylation assays as biochemical diagnostic tools for leukodystrophies.
André C, Martiel I, Wolff P, Landolfo M, Lorber B, da Veiga C Silva, Dejaegere A, Dumas P, Guichard G, Olieric V, Wagner J G, Burnouf D Y
Interaction of a Model Peptide on Gram Negative and Gram Positive Bacterial Sliding Clamps Article de journal
Dans: ACS Infect Dis, vol. 5, no. 6, p. 1022-1034, 2019, ISBN: 30912430.
Résumé | Liens | BibTeX | Étiquettes: ARN-MS, ENNIFAR, FRUGIER, ITC ligand−target interaction new antibacterials development sliding clamp, Unité ARN
@article{,
title = {Interaction of a Model Peptide on Gram Negative and Gram Positive Bacterial Sliding Clamps},
author = {C André and I Martiel and P Wolff and M Landolfo and B Lorber and C Silva da Veiga and A Dejaegere and P Dumas and G Guichard and V Olieric and J G Wagner and D Y Burnouf},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30912430?dopt=Abstract},
doi = {10.1021/acsinfecdis.9b00089},
isbn = {30912430},
year = {2019},
date = {2019-01-01},
urldate = {2019-01-01},
journal = {ACS Infect Dis},
volume = {5},
number = {6},
pages = {1022-1034},
abstract = {Bacterial sliding clamps control the access of DNA polymerases to the replication fork and are appealing targets for antibacterial drugs development. It is therefore essential to decipher the polymerase-clamp binding mode across various bacterial species. Here, two residues of the E. coli clamp binding pocket, EcS346 and EcM362, and their cognate residues in M. tuberculosis and B. subtilis clamps, were mutated. The effects of these mutations on the interaction of a model peptide with these variant clamps were evaluated by thermodynamic, molecular dynamics, X-rays crystallography and biochemical analyses. EcM362 and corresponding residues in Gram positive clamps occupy a strategic position where a mobile residue is essential for an efficient peptide interaction. EcS346 has a more subtle function that modulates the pocket folding dynamics, while the equivalent residue in B. subtilis is essential for polymerase activity and might therefore be a Gram positive specific molecular marker. Finally, the peptide binds through an induced-fit process to Gram negative and positive pockets but the complex stability varies according to a pocket specific network of interactions.},
keywords = {ARN-MS, ENNIFAR, FRUGIER, ITC ligand−target interaction new antibacterials development sliding clamp, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2018
Riley L G, Heeney M M, Rudinger-Thirion J, Frugier M, Campagna D R, Zhou R, Hale G A, Hilliard L M, Kaplan J A, Kwiatkowski J L, Sieff C A, Steensma D P, Rennings A J, Simons A, Schaap N, Roodenburg R J, Kleefstra T, Arenillas L, Fita-Torró J, Ahmed R, Abboud M, Bechara E, Farah R, Tamminga R Y, Bottomley S S, Sanchez M, Swinkels D W, Christodoulou J, Fleming M D
The phenotypic spectrum of germline YARS2 variants: from isolated sideroblastic anemia to mitochondrial myopathy, lactic acidosis and sideroblastic anemia 2 Article de journal
Dans: Haematologica, vol. 103, no. 12, p. 2008-2015, 2018, ISBN: 30026338.
Résumé | Liens | BibTeX | Étiquettes: Congenital sideroblastic anemia MLASA YARS2 mitochondrial myopathy sideroblastic anemia, FRUGIER, Unité ARN
@article{,
title = {The phenotypic spectrum of germline YARS2 variants: from isolated sideroblastic anemia to mitochondrial myopathy, lactic acidosis and sideroblastic anemia 2},
author = {L G Riley and M M Heeney and J Rudinger-Thirion and M Frugier and D R Campagna and R Zhou and G A Hale and L M Hilliard and J A Kaplan and J L Kwiatkowski and C A Sieff and D P Steensma and A J Rennings and A Simons and N Schaap and R J Roodenburg and T Kleefstra and L Arenillas and J Fita-Torró and R Ahmed and M Abboud and E Bechara and R Farah and R Y Tamminga and S S Bottomley and M Sanchez and D W Swinkels and J Christodoulou and M D Fleming},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30026338},
doi = {10.3324/haematol.2017.182659},
isbn = {30026338},
year = {2018},
date = {2018-01-01},
journal = {Haematologica},
volume = {103},
number = {12},
pages = {2008-2015},
abstract = {YARS2 variants have previously been described in patients with myopathy, lactic acidosis and sideroblastic anemia 2 (MLASA2). YARS2 encodes the mitochondrial tyrosyl-tRNA synthetase, which is responsible for conjugating tyrosine to its cognate mt-tRNA for mitochondrial protein synthesis. Here we describe 14 individuals from 11 families presenting with sideroblastic anemia and with YARS2 variants that we identified using a sideroblastic anemia gene panel or exome sequencing. The phenotype of these patients ranged from MLASA to isolated congenital sideroblastic anemia. As in previous cases, inter- and intra-familial phenotypic variability was observed, however this report includes the first cases with isolated sideroblastic anemia and patients with biallelic YARS2 variants that have no clinically ascertainable phenotype. We identified ten novel YARS2 variants and three previously reported variants. In vitro amino-acylation assays of three five novel missense variants showed they that three had less effect on the catalytic activity of YARS2 than the most commonly reported variant, p.(Phe52Leu), associated with MLASA2, which may explain the milder phenotypes in patients with these variants. However, the other two missense variants had a more severe effect on YARS2 catalytic efficiency. Several patients carried the common YARS2 c.572 G>T, p.(Gly191Val) variant (minor allele frequency = 0.1259) in trans with a rare deleterious YARS2 variant. We have previously shown that the p.(Gly191Val) variant reduces YARS2 catalytic activity. Consequently, we suggest that biallelic YARS2 variants, including severe loss-of-function alleles in trans of the common p.(Gly191Val) variant, should be considered as a cause of isolated congenital sideroblastic anemia, as well as the MLASA syndromic phenotype.},
keywords = {Congenital sideroblastic anemia MLASA YARS2 mitochondrial myopathy sideroblastic anemia, FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Cela M, Paulus C, Santos M A S, Moura G R, Frugier M, Rudinger-Thirion J
Plasmodium apicoplast tyrosyl-tRNA synthetase recognizes an unusual, simplified identity set in cognate tRNATyr Article de journal
Dans: PLoS One, vol. 13, no. 12, p. e0209805, 2018, ISBN: 30592748.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{,
title = {Plasmodium apicoplast tyrosyl-tRNA synthetase recognizes an unusual, simplified identity set in cognate tRNATyr},
author = {M Cela and C Paulus and M A S Santos and G R Moura and M Frugier and J Rudinger-Thirion},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30592748?dopt=Abstract},
doi = {10.1371/journal.pone.0209805},
isbn = {30592748},
year = {2018},
date = {2018-01-01},
journal = {PLoS One},
volume = {13},
number = {12},
pages = {e0209805},
abstract = {The life cycle of Plasmodium falciparum, the agent responsible for malaria, depends on both cytosolic and apicoplast translation fidelity. Apicoplast aminoacyl-tRNA synthetases (aaRS) are bacterial-like enzymes devoted to organellar tRNA aminoacylation. They are all encoded by the nuclear genome and are translocated into the apicoplast only after cytosolic biosynthesis. Apicoplast aaRSs contain numerous idiosyncratic sequence insertions: An understanding of the roles of these insertions has remained elusive and they hinder efforts to heterologously overexpress these proteins. Moreover, the A/T rich content of the Plasmodium genome leads to A/U rich apicoplast tRNA substrates that display structural plasticity. Here, we focus on the P. falciparum apicoplast tyrosyl-tRNA synthetase (Pf-apiTyrRS) and its cognate tRNATyr substrate (Pf-apitRNATyr). Cloning and expression strategies used to obtain an active and functional recombinant Pf-apiTyrRS are reported. Functional analyses established that only three weak identity elements in the apitRNATyr promote specific recognition by the cognate Pf-apiTyrRS and that positive identity elements usually found in the tRNATyr acceptor stem are excluded from this set. This finding brings to light an unusual behavior for a tRNATyr aminoacylation system and suggests that Pf-apiTyrRS uses primarily negative recognition elements to direct tyrosylation specificity.},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Hemmer C, Djennane S, Ackerer L, Hleibieh K, Marmonier A, Gersch S, Garcia S, Vigne E, Komar V, Perrin M, Gertz C, Belval L, Berthold F, Monsion B, Schmitt-Keichinger C, Lemaire O, Lorber B, Gutiérrez C, Muyldermans S, Demangeat G, Ritzenthaler C
Nanobody-mediated resistance to Grapevine fanleaf virus in plants. Article de journal
Dans: Plant Biotechnol J, vol. 16, no. 2, p. 660-671, 2018, ISBN: 28796912.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, GMO Nanobodies Single chain antibodies grapevine nepovirus plant virus transgenic plant, Unité ARN
@article{,
title = {Nanobody-mediated resistance to Grapevine fanleaf virus in plants.},
author = {C Hemmer and S Djennane and L Ackerer and K Hleibieh and A Marmonier and S Gersch and S Garcia and E Vigne and V Komar and M Perrin and C Gertz and L Belval and F Berthold and B Monsion and C Schmitt-Keichinger and O Lemaire and B Lorber and C Gutiérrez and S Muyldermans and G Demangeat and C Ritzenthaler},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28796912?dopt=Abstract},
doi = {10.1111/pbi.12819},
isbn = {28796912},
year = {2018},
date = {2018-01-01},
journal = {Plant Biotechnol J},
volume = {16},
number = {2},
pages = {660-671},
abstract = {Since their discovery, single-domain antigen-binding fragments of camelid-derived heavy chain-only antibodies, also known as Nanobodies (Nbs), have proven to be of outstanding interest as therapeutics against human diseases and pathogens including viruses, but their use against phytopathogens remains limited. Many plant viruses including Grapevine fanleaf virus (GFLV), a nematode-transmitted icosahedral virus and causal agent of fanleaf degenerative disease, have worldwide distribution and huge burden on crop yields representing billions of US dollars of losses annually, yet solutions to combat these viruses are often limited or inefficient. Here we identified a Nb specific to GFLV that confers strong resistance to GFLV upon stable expression in the model plant Nicotiana benthamiana and also in grapevine rootstock, the natural host of the virus. We showed that resistance was effective against a broad range of GFLV isolates independently of the inoculation method including upon nematode transmission but not against its close relative, Arabis mosaic virus. We also demonstrated that virus neutralization occurs at an early step of the virus life cycle, prior to cell-to-cell movement. Our findings will not only be instrumental to confer resistance to GFLV in grapevine but more generally they pave the way for the generation of novel antiviral strategies in plants based on Nbs. This article is protected by copyright. All rights reserved.},
keywords = {FRUGIER, GMO Nanobodies Single chain antibodies grapevine nepovirus plant virus transgenic plant, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2016
Riley L G, Rudinger-Thirion J, Schmitz-Abe K, Thorburn D R, Davis R L, Teo J, Arbuckle S, Cooper S T, Campagna D R, Frugier M, Markianos K, Sue C M, Fleming M D, Christodoulou J
LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure. Chapitre d'ouvrage
Dans: Morava, E (Ed.): JIMD Rep, vol. 28, p. 49-57, Springer, SSIEM, 2016, ISBN: 26537577.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@inbook{,
title = {LARS2 Variants Associated with Hydrops, Lactic Acidosis, Sideroblastic Anemia, and Multisystem Failure.},
author = {L G Riley and J Rudinger-Thirion and K Schmitz-Abe and D R Thorburn and R L Davis and J Teo and S Arbuckle and S T Cooper and D R Campagna and M Frugier and K Markianos and C M Sue and M D Fleming and J Christodoulou},
editor = {E Morava},
url = {http://www.ncbi.nlm.nih.gov/pubmed/26537577?dopt=Abstract},
doi = {10.1007/8904_2015_515},
isbn = {26537577},
year = {2016},
date = {2016-01-01},
booktitle = {JIMD Rep},
volume = {28},
pages = {49-57},
publisher = {Springer},
edition = {SSIEM},
abstract = {Pathogenic variants in mitochondrial aminoacyl-tRNA synthetases result in a broad range of mitochondrial respiratory chain disorders despite their shared role in mitochondrial protein synthesis. LARS2 encodes the mitochondrial leucyl-tRNA synthetase, which attaches leucine to its cognate tRNA. Sequence variants in LARS2 have previously been associated with Perrault syndrome, characterized by premature ovarian failure and hearing loss (OMIM #615300). In this study, we report variants in LARS2 that are associated with a severe multisystem metabolic disorder. The proband was born prematurely with severe lactic acidosis, hydrops, and sideroblastic anemia. She had multisystem complications with hyaline membrane disease, impaired cardiac function, a coagulopathy, pulmonary hypertension, and progressive renal disease and succumbed at 5 days of age. Whole exome sequencing of patient DNA revealed compound heterozygous variants in LARS2 (c.1289C>T; p.Ala430Val and c.1565C>A; p.Thr522Asn). The c.1565C>A (p.Thr522Asn) LARS2 variant has previously been associated with Perrault syndrome and both identified variants are predicted to be damaging (SIFT, PolyPhen). Muscle and liver samples from the proband did not display marked mitochondrial respiratory chain enzyme deficiency. Immunoblotting of patient muscle and liver showed LARS2 levels were reduced in liver and complex I protein levels were reduced in patient muscle and liver. Aminoacylation assays revealed p.Ala430Val LARS2 had an 18-fold loss of catalytic efficiency and p.Thr522Asn a 9-fold loss compared to wild-type LARS2. We suggest that the identified LARS2 variants are responsible for the severe multisystem clinical phenotype seen in this baby and that mutations in LARS2 can result in variable phenotypes.},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {inbook}
}
Kapps D, Cela M, Théobald-Dietrich A, Hendrickson T, Frugier M
OB or Not OB: Idiosyncratic utilization of the tRNA-binding OB-fold domain in unicellular, pathogenic eukaryotes. Article de journal
Dans: FEBS Lett, vol. 590, no. 23, p. 4180-4191, 2016, ISBN: 27714804.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Trbp111 parasites pathogenic eukaryotes tRNA binding protein, Unité ARN
@article{,
title = {OB or Not OB: Idiosyncratic utilization of the tRNA-binding OB-fold domain in unicellular, pathogenic eukaryotes.},
author = {D Kapps and M Cela and A Théobald-Dietrich and T Hendrickson and M Frugier},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27714804?dopt=Abstract},
doi = {10.1002/1873-3468.12441},
isbn = {27714804},
year = {2016},
date = {2016-01-01},
journal = {FEBS Lett},
volume = {590},
number = {23},
pages = {4180-4191},
abstract = {In this Review, we examine the so-called 'OB-fold', a tRNA-binding domain homologous to the bacterial tRNA-binding protein Trbp111. We highlight the ability of OB-fold homologs to bind tRNAs and summarize their distribution in evolution. Nature has capitalized on the advantageous effects acquired when an OB-fold domain binds to tRNA by evolutionarily selecting this domain for fusion to different enzymes. Here, we review our current understanding of how the complexity of OB-fold containing proteins and enzymes developed to expand their functions, especially in unicellular, pathogenic eukaryotes. This article is protected by copyright. All rights reserved.},
keywords = {FRUGIER, Trbp111 parasites pathogenic eukaryotes tRNA binding protein, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Bour T, Mahmoudi N, Kapps D, Thiberge S, Bargieri D, Ménard R, Frugier M
Apicomplexa-specific tRip facilitates import of exogenous tRNAs into malaria parasites Article de journal
Dans: Proc Natl Acad Sci U S A, vol. 113, no. 17, p. 4717-4722, 2016, ISBN: 27071116.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Plasmodium tRNA trafficking, Unité ARN
@article{,
title = {Apicomplexa-specific tRip facilitates import of exogenous tRNAs into malaria parasites},
author = {T Bour and N Mahmoudi and D Kapps and S Thiberge and D Bargieri and R Ménard and M Frugier},
url = {http://www.ncbi.nlm.nih.gov/pubmed/27071116},
doi = {10.1073/pnas.1600476113},
isbn = {27071116},
year = {2016},
date = {2016-01-01},
journal = {Proc Natl Acad Sci U S A},
volume = {113},
number = {17},
pages = {4717-4722},
abstract = {The malaria-causingPlasmodiumparasites are transmitted to vertebrates by mosquitoes. To support their growth and replication, these intracellular parasites, which belong to the phylumApicomplexa,have developed mechanisms to exploit their hosts. These mechanisms include expropriation of small metabolites from infected host cells, such as purine nucleotides and amino acids. Heretofore, no evidence suggested that transfer RNAs (tRNAs) could also be exploited. We identified an unusual gene inApicomplexawith a coding sequence for membrane-docking and structure-specific tRNA binding. ThisApicomplexaprotein-designated tRip (tRNA import protein)-is anchored to the parasite plasma membrane and directs import of exogenous tRNAs. In the absence of tRip, the fitness of the parasite stage that multiplies in the blood is significantly reduced, indicating that the parasite may need host tRNAs to sustain its own translation and/or as regulatory RNAs.Plasmodiumis thus the first example, to our knowledge, of a cell importing exogenous tRNAs, suggesting a remarkable adaptation of this parasite to extend its reach into host cell biology.},
keywords = {FRUGIER, Plasmodium tRNA trafficking, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2015
Alexandrova J, Paulus C, Rudinger-Thirion J, Jossinet F, Frugier M
Elaborate uORF/IRES features control expression and localization of human glycyl-tRNA synthetase. Article de journal
Dans: RNA Biol, vol. 12, no. 12, p. 1301-1313, 2015, ISBN: 26327585.
Résumé | Liens | BibTeX | Étiquettes: Aminoacyl-tRNA synthetase IRES post-transcriptional control uORF, FRUGIER, Unité ARN
@article{,
title = {Elaborate uORF/IRES features control expression and localization of human glycyl-tRNA synthetase.},
author = {J Alexandrova and C Paulus and J Rudinger-Thirion and F Jossinet and M Frugier},
url = {http://www.ncbi.nlm.nih.gov/pubmed/26327585?dopt=Abstract},
doi = {10.1080/15476286.2015.1086866},
isbn = {26327585},
year = {2015},
date = {2015-01-01},
journal = {RNA Biol},
volume = {12},
number = {12},
pages = {1301-1313},
abstract = {The canonical activity of glycyl-tRNA synthetase (GARS) is to charge glycine onto its cognate tRNAs. However, outside translation, GARS also participates in many other functions. A single gene encodes both the cytosolic and mitochondrial forms of GARS but two mRNA isoforms were identified. Using immunolocalization assays, in vitro translation assays and bicistronic constructs we provide experimental evidence that one of these mRNAs tightly controls expression and localization of human GARS. An intricate regulatory domain was found in its 5'-UTR which displays a functional Internal Ribosome Entry Site and an upstream Open Reading Frame. Together, these elements hinder the synthesis of the mitochondrial GARS and target the translation of the cytosolic enzyme to ER-bound ribosomes. This finding reveals a complex picture of GARS translation and localization in mammals. In this context, we discuss how human GARS expression could influence its moonlighting activities and its involvement in diseases.},
keywords = {Aminoacyl-tRNA synthetase IRES post-transcriptional control uORF, FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2014
Wolff P, Amal I, Oliéric V, Chaloin O, Gygli G, Ennifar E, Lorber B, Guichard G, Wagner J E, Dejaegere A, Burnouf D Y
Differential Modes of Peptide Binding onto Replicative Sliding Clamps from Various Bacterial Origins. Article de journal
Dans: J Med Chem, vol. 57, no. 18, p. 7565-7576, 2014, ISBN: 25170813.
Résumé | Liens | BibTeX | Étiquettes: ENNIFAR, FRUGIER, Unité ARN
@article{,
title = {Differential Modes of Peptide Binding onto Replicative Sliding Clamps from Various Bacterial Origins.},
author = {P Wolff and I Amal and V Oliéric and O Chaloin and G Gygli and E Ennifar and B Lorber and G Guichard and J E Wagner and A Dejaegere and D Y Burnouf},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25170813?dopt=Abstract},
doi = {10.1021/jm500467a},
isbn = {25170813},
year = {2014},
date = {2014-01-01},
journal = {J Med Chem},
volume = {57},
number = {18},
pages = {7565-7576},
abstract = {Bacterial sliding clamps are molecular hubs that interact with many proteins involved in DNA metabolism through their binding, via a conserved peptidic sequence, into a universally conserved pocket. This interacting pocket is acknowledged as a potential molecular target for the development of new antibiotics. We previously designed short peptides with an improved affinity for the Escherichia coli binding pocket. Here we show that these peptides differentially interact with other bacterial clamps, despite the fact that all pockets are structurally similar. Thermodynamic and modeling analyses of the interactions differentiate between two categories of clamps: group I clamps interacts efficiently with our designed peptides and assembles the Escherichia coli and related orthologs clamps, while group II poorly interact with the same peptides and includes Bacillus subtilis and other Gram+ clamps. These studies also suggest that the peptide binding process could occur via different mechanisms depending on which type of clamp it binds to.},
keywords = {ENNIFAR, FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2013
Neuenfeldt A, Lorber B, Ennifar E, Gaudry A, Sauter C, Sissler M, Florentz C
Thermodynamic properties distinguish human mitochondrial aspartyl-tRNA synthetase from bacterial homolog with same 3D architecture Article de journal
Dans: Nucleic Acids Research, vol. 41, no. 4, p. 2698-708, 2013.
Résumé | Liens | BibTeX | Étiquettes: ENNIFAR, FRUGIER, SAUTER, Unité ARN
@article{Neuenfeldt2013,
title = {Thermodynamic properties distinguish human mitochondrial aspartyl-tRNA synthetase from bacterial homolog with same 3D architecture},
author = {A Neuenfeldt and B Lorber and E Ennifar and A Gaudry and C Sauter and M Sissler and C Florentz
},
url = {https://pubmed.ncbi.nlm.nih.gov/23275545/},
doi = { 10.1093/nar/gks1322 },
year = {2013},
date = {2013-02-04},
journal = {Nucleic Acids Research},
volume = {41},
number = {4},
pages = {2698-708},
abstract = {In the mammalian mitochondrial translation apparatus, the proteins and their partner RNAs are coded by two genomes. The proteins are nuclear-encoded and resemble their homologs, whereas the RNAs coming from the rapidly evolving mitochondrial genome have lost critical structural information. This raises the question of molecular adaptation of these proteins to their peculiar partner RNAs. The crystal structure of the homodimeric bacterial-type human mitochondrial aspartyl-tRNA synthetase (DRS) confirmed a 3D architecture close to that of Escherichia coli DRS. However, the mitochondrial enzyme distinguishes by an enlarged catalytic groove, a more electropositive surface potential and an alternate interaction network at the subunits interface. It also presented a thermal stability reduced by as much as 12°C. Isothermal titration calorimetry analyses revealed that the affinity of the mitochondrial enzyme for cognate and non-cognate tRNAs is one order of magnitude higher, but with different enthalpy and entropy contributions. They further indicated that both enzymes bind an adenylate analog by a cooperative allosteric mechanism with different thermodynamic contributions. The larger flexibility of the mitochondrial synthetase with respect to the bacterial enzyme, in combination with a preserved architecture, may represent an evolutionary process, allowing nuclear-encoded proteins to cooperate with degenerated organelle RNAs. },
keywords = {ENNIFAR, FRUGIER, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2012
Gaudry A, Lorber B, Neuenfeldt A, Sauter C, Florentz C, Sissler M
Re-designed N-terminus enhances expression, solubility and crystallizability of mitochondrial protein. Article de journal
Dans: Protein Eng Des Sel, vol. 25, no. 9, p. 473-481, 2012, ISBN: 22871419.
Résumé | Liens | BibTeX | Étiquettes: FLORENTZ, FRUGIER, SAUTER, SISSLER, Unité ARN
@article{,
title = {Re-designed N-terminus enhances expression, solubility and crystallizability of mitochondrial protein.},
author = {A Gaudry and B Lorber and A Neuenfeldt and C Sauter and C Florentz and M Sissler},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22871419?report=&dispmax=200&tool=PubCrawler_2.23},
isbn = {22871419},
year = {2012},
date = {2012-01-01},
journal = {Protein Eng Des Sel},
volume = {25},
number = {9},
pages = {473-481},
abstract = {Mitochondrial aminoacyl-tRNA synthetases are key enzymes in translation. They are encoded by the nuclear genome, synthesized as precursors in the cytosol and imported. Most are matured by cleavage of their N-terminal targeting sequence. The poor expression of mature proteins in prokaryotic systems, along with their low solubility and stability after purification are major obstacles for biophysical and crystallographic studies. The purpose of the present work was to analyze the influence of additives on a slightly soluble aspartyl-tRNA synthetase and of the N-terminal sequence of the protein on its expression and solubility. On the one hand, the solubility of the enzyme was augmented to some extent in the presence of a chemical analog of the intermediary product aspartyl-adenylate, 5'-O-[N-(L aspartyl) sulfamoyl] adenosine. On the other hand, expression was enhanced by extending the N-terminus by seven natural amino acids from the predicted targeting sequence. The re-designed enzyme was active, monodisperse, more soluble and yielded crystals that are suitable for structure determination. This result underlines the importance of the N-terminal residue sequence for solubility. It suggests that additional criteria should be taken into account for the prediction of cleavage sites in mitochondrial targeting sequences.},
keywords = {FLORENTZ, FRUGIER, SAUTER, SISSLER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Giege R, Juhling F, Putz J, Stadler P, Sauter C, Florentz C
Structure of transfer RNAs: similarity and variability Article de journal
Dans: Wiley Interdiscip Rev RNA, vol. 3, no. 1, p. 37-61, 2012, ISBN: 21957054.
Résumé | Liens | BibTeX | Étiquettes: FLORENTZ, FRUGIER, SAUTER, Unité ARN
@article{,
title = {Structure of transfer RNAs: similarity and variability},
author = {R Giege and F Juhling and J Putz and P Stadler and C Sauter and C Florentz},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21957054?dopt=Abstrac},
doi = {10.1002/wrna.103},
isbn = {21957054},
year = {2012},
date = {2012-01-01},
journal = {Wiley Interdiscip Rev RNA},
volume = {3},
number = {1},
pages = {37-61},
abstract = {Transfer RNAs (tRNAs) are ancient molecules whose origin goes back to the beginning of life on Earth. Key partners in the ribosome-translation machinery, tRNAs read genetic information on messenger RNA and deliver codon specified amino acids attached to their distal 3′-extremity for peptide bond synthesis on the ribosome. In addition to this universal function, tRNAs participate in a wealth of other biological processes and undergo intricate maturation events. Our understanding of tRNA biology has been mainly phenomenological, but ongoing progress in structural biology is giving a robust physico-chemical basis that explains many facets of tRNA functions. Advanced sequence analysis of tRNA genes and their RNA transcripts have uncovered rules that underly tRNA 2D folding and 3D L-shaped architecture, as well as provided clues about their evolution. The increasing number of X-ray structures of free, protein- and ribosome-bound tRNA, reveal structural details accounting for the identity of the 22 tRNA families (one for each proteinogenic amino acid) and for the multifunctionality of a given family. Importantly, the structural role of post-transcriptional tRNA modifications is being deciphered. On the other hand, the plasticity of tRNA structure during function has been illustrated using a variety of technical approaches that allow dynamical insights. The large range of structural properties not only allows tRNAs to be the key actors of translation, but also sustain a diversity of unrelated functions from which only a few have already been pinpointed. Many surprises can still be expected. WIREs RNA 2012, 3:3761. doi: 10.1002/wrna.103},
keywords = {FLORENTZ, FRUGIER, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Lorber B, Fischer F, Bailly M, Roy H, Kern D
Protein analysis by dynamic light scattering: Methods and techniques for students. Article de journal
Dans: Biochem Mol Biol Educ, vol. 40, no. 6, p. 372-382, 2012, ISBN: 23166025.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{,
title = {Protein analysis by dynamic light scattering: Methods and techniques for students.},
author = {B Lorber and F Fischer and M Bailly and H Roy and D Kern},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23166025},
doi = {10.1002/bmb.20644},
isbn = {23166025},
year = {2012},
date = {2012-01-01},
journal = {Biochem Mol Biol Educ},
volume = {40},
number = {6},
pages = {372-382},
abstract = {Dynamic light scattering (DLS) analyses are routinely used in biology laboratories to detect aggregates in macromolecular solutions, to determine the size of proteins, nucleic acids, and complexes or to monitor the binding of ligands. This article is written for graduate and undergraduate students with access to DLS and for faculty members who wish to incorporate DLS into a lab activity, a practical course or research. It reviews the basic concepts of light scattering measurements and addresses four critical aspects of the analysis and interpretation of DLS results. To ensure reproducible quantitative data, attention should be paid to controlling the preparation and handling of proteins or assemblies because variations in the state of aggregation, induced by minor changes in experimental condition or technique, might compromise DLS results and affect protein activity. Variables like temperature, solvent viscosity, and inter-particle interactions may also influence particle size determination. Every point is illustrated by case studies, including a commercially available albumin, a small RNA virus isolated from plants, as well as four soluble proteins and a ribonucleoprotein assembly purified and characterized by students in the frame of their master degree. © 2012 by The International Union of Biochemistry and Molecular Biology.},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2011
Rudinger-Thirion J, Lescure A, Paulus C, Frugier M
Misfolded human tRNA isodecoder binds and neutralizes a 3' UTR-embedded Alu element Article de journal
Dans: Proc Natl Acad Sci U S A, vol. 108, no. 40, p. E794-802, 2011, ISSN: 1091-6490 (Electronic) 0027-8424 (Linking), (Rudinger-Thirion, Joelle Lescure, Alain Paulus, Caroline Frugier, Magali United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):E794-802. Epub 2011 Sep 6.).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, LESCURE, Unité ARN
@article{,
title = {Misfolded human tRNA isodecoder binds and neutralizes a 3' UTR-embedded Alu element},
author = {J Rudinger-Thirion and A Lescure and C Paulus and M Frugier},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21896722},
doi = {10.1073/pnas.1103698108},
issn = {1091-6490 (Electronic) 0027-8424 (Linking)},
year = {2011},
date = {2011-01-01},
journal = {Proc Natl Acad Sci U S A},
volume = {108},
number = {40},
pages = {E794-802},
abstract = {Several classes of small noncoding RNAs are key players in cellular metabolism including mRNA decoding, RNA processing, and mRNA stability. Here we show that a tRNA(Asp) isodecoder, corresponding to a human tRNA-derived sequence, binds to an embedded Alu RNA element contained in the 3' UTR of the human aspartyl-tRNA synthetase mRNA. This interaction between two well-known classes of RNA molecules, tRNA and Alu RNA, is driven by an unexpected structural motif and induces a global rearrangement of the 3' UTR. Besides, this 3' UTR contains two functional polyadenylation signals. We propose a model where the tRNA/Alu interaction would modulate the accessibility of the two alternative polyadenylation sites and regulate the stability of the mRNA. This unique regulation mechanism would link gene expression to RNA polymerase III transcription and may have implications in a primate-specific signal pathway.},
note = {Rudinger-Thirion, Joelle
Lescure, Alain
Paulus, Caroline
Frugier, Magali
United States
Proceedings of the National Academy of Sciences of the United States of America
Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):E794-802. Epub 2011 Sep 6.},
keywords = {FRUGIER, LESCURE, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Schellenberger P, Demangeat G, Lemaire O, Ritzenthaler C, Bergdoll M, Olieric V, Sauter C, Lorber B
Strategies for the crystallization of viruses: Using phase diagrams and gels to produce 3D crystals of Grapevine fanleaf virus Article de journal
Dans: J Struct Biol, vol. 174, no. 2, p. 344-351, 2011, ISSN: 1095-8657 (Electronic) 1047-8477 (Linking), (Schellenberger, Pascale Demangeat, Gerard Lemaire, Olivier Ritzenthaler, Christophe Bergdoll, Marc Olieric, Vincent Sauter, Claude Lorber, Bernard United States Journal of structural biology J Struct Biol. 2011 May;174(2):344-51. Epub 2011 Feb 23.).
Résumé | Liens | BibTeX | Étiquettes: FLORENTZ, FRUGIER, SAUTER, Unité ARN
@article{,
title = {Strategies for the crystallization of viruses: Using phase diagrams and gels to produce 3D crystals of Grapevine fanleaf virus},
author = {P Schellenberger and G Demangeat and O Lemaire and C Ritzenthaler and M Bergdoll and V Olieric and C Sauter and B Lorber},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21352920},
doi = {10.1016/j.jsb.2011.02.007},
issn = {1095-8657 (Electronic) 1047-8477 (Linking)},
year = {2011},
date = {2011-01-01},
journal = {J Struct Biol},
volume = {174},
number = {2},
pages = {344-351},
abstract = {The small icosahedral plant RNA nepovirus Grapevine fanleaf virus (GFLV) is specifically transmitted by a nematode and causes major damage to vineyards worldwide. To elucidate the molecular mechanisms underlying the recognition between the surface of its protein capsid and cellular components of its vector, host and viral proteins synthesized upon infection, the wild type GFLV strain F13 and a natural mutant (GFLV-TD) carrying a Gly(297)Asp mutation were purified, characterized and crystallized. Subsequently, the geometry and volume of their crystals was optimized by establishing phase diagrams. GFLV-TD was twice as soluble as the parent virus in the crystallization solution and its crystals diffracted X-rays to a resolution of 2.7A. The diffraction limit of GFLV-F13 crystals was extended from 5.5 to 3A by growth in agarose gel. Preliminary crystallographic analyses indicate that both types of crystals are suitable for structure determination. Keys for the successful production of GFLV crystals include the rigorous quality control of virus preparations, crystal quality improvement using phase diagrams, and crystal lattice reinforcement by growth in agarose gel. These strategies are applicable to the production of well-diffracting crystals of other viruses and macromolecular assemblies.},
note = {Schellenberger, Pascale
Demangeat, Gerard
Lemaire, Olivier
Ritzenthaler, Christophe
Bergdoll, Marc
Olieric, Vincent
Sauter, Claude
Lorber, Bernard
United States
Journal of structural biology
J Struct Biol. 2011 May;174(2):344-51. Epub 2011 Feb 23.},
keywords = {FLORENTZ, FRUGIER, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Schellenberger P, Sauter C, Lorber B, Bron P, Trapani S, Bergdoll M, Marmonier A, Schmitt-Kelchinger C, Lemaire O, Demangeat G, Ritzenthaler C
Structural insights into viral determinants of nematode mediated Grapevine fanleaf virus transmission. Article de journal
Dans: PLoS Pathog, vol. 7, no. 5, p. e1002034, 2011, ISBN: 21625570.
Résumé | Liens | BibTeX | Étiquettes: FLORENTZ, FRUGIER, SAUTER, Unité ARN
@article{,
title = {Structural insights into viral determinants of nematode mediated Grapevine fanleaf virus transmission.},
author = {P Schellenberger and C Sauter and B Lorber and P Bron and S Trapani and M Bergdoll and A Marmonier and C Schmitt-Kelchinger and O Lemaire and G Demangeat and C Ritzenthaler},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21625570},
doi = {10.1371/journal.ppat.1002034},
isbn = {21625570},
year = {2011},
date = {2011-01-01},
journal = {PLoS Pathog},
volume = {7},
number = {5},
pages = {e1002034},
abstract = {Many animal and plant viruses rely on vectors for their transmission from host to host. Grapevine fanleaf virus (GFLV), a picorna-like virus from plants, is transmitted specifically by the ectoparasitic nematode Xiphinema index. The icosahedral capsid of GFLV, which consists of 60 identical coat protein subunits (CP), carries the determinants of this specificity. Here, we provide novel insight into GFLV transmission by nematodes through a comparative structural and functional analysis of two GFLV variants. We isolated a mutant GFLV strain (GFLV-TD) poorly transmissible by nematodes, and showed that the transmission defect is due to a glycine to aspartate mutation at position 297 (Gly297Asp) in the CP. We next determined the crystal structures of the wild-type GFLV strain F13 at 3.0 Å and of GFLV-TD at 2.7 Å resolution. The Gly297Asp mutation mapped to an exposed loop at the outer surface of the capsid and did not affect the conformation of the assembled capsid, nor of individual CP molecules. The loop is part of a positively charged pocket that includes a previously identified determinant of transmission. We propose that this pocket is a ligand-binding site with essential function in GFLV transmission by X. index. Our data suggest that perturbation of the electrostatic landscape of this pocket affects the interaction of the virion with specific receptors of the nematode's feeding apparatus, and thereby severely diminishes its transmission efficiency. These data provide a first structural insight into the interactions between a plant virus and a nematode vector.},
keywords = {FLORENTZ, FRUGIER, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2009
Bour T, Akaddar A, Lorber B, Blais S, Balg C, Candolfi E, Frugier M
Plasmodial aspartyl-tRNA synthetases and peculiarities in Plasmodium falciparum Article de journal
Dans: J Biol Chem, vol. 284, no. 28, p. 18893-18903, 2009, ISBN: 19443655, (0021-9258 (Print) 0021-9258 (Linking) Journal Article Research Support, Non-U.S. Gov't).
Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Amino Acid Sequence Amino Acids/chemistry Animals Aspartate-tRNA Ligase/*metabolism Aspartic Acid/chemistry Base Sequence Cloning, FRUGIER, Molecular Cytoplasm/metabolism Dimerization Fungal Proteins/chemistry Humans Kinetics Molecular Sequence Data Plasmodium falciparum Protein Structure, Tertiary Sequence Homology, Unité ARN
@article{,
title = {Plasmodial aspartyl-tRNA synthetases and peculiarities in Plasmodium falciparum},
author = {T Bour and A Akaddar and B Lorber and S Blais and C Balg and E Candolfi and M Frugier},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19443655},
isbn = {19443655},
year = {2009},
date = {2009-01-01},
journal = {J Biol Chem},
volume = {284},
number = {28},
pages = {18893-18903},
abstract = {Distinctive features of aspartyl-transfer RNA (tRNA) synthetases (AspRS) from the protozoan Plasmodium genus are described. These apicomplexan AspRSs contain 29-31 amino acid insertions in their anticodon binding domains, a remarkably long N-terminal appendix that varies in size from 110 to 165 amino acids and two potential initiation codons. This article focuses on the atypical functional and structural properties of Plasmodium falciparum cytosolic AspRS, the causative parasite of human malaria. This species encodes a 626 or 577 amino acids AspRS depending on whether initiation starts on the first or second in-frame initiation codon. The longer protein has poor solubility and a propensity to aggregate. Production of the short version was favored as shown by the comparison of the recombinant protein with endogenous AspRS. Comparison of the tRNA aminoacylation activity of wild-type and mutant parasite AspRSs with those of yeast and human AspRSs revealed unique properties. The N-terminal extension contains a motif that provides unexpectedly strong RNA binding to plasmodial AspRS. Furthermore, experiments demonstrated the requirement of the plasmodial insertion for AspRS dimerization and, therefore, tRNA aminoacylation and other putative functions. Implications for the parasite biology are proposed. These data provide a robust background for unraveling the precise functional properties of the parasite AspRS and for developing novel lead compounds against malaria, targeting its idiosyncratic domains.},
note = {0021-9258 (Print)
0021-9258 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {Amino Acid, Amino Acid Sequence Amino Acids/chemistry Animals Aspartate-tRNA Ligase/*metabolism Aspartic Acid/chemistry Base Sequence Cloning, FRUGIER, Molecular Cytoplasm/metabolism Dimerization Fungal Proteins/chemistry Humans Kinetics Molecular Sequence Data Plasmodium falciparum Protein Structure, Tertiary Sequence Homology, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Sauter C, Balg C, Moreno A, Dhouib K, Théobald-Dietrich A, Chenevert R, Giege R, Lorber B
Agarose gel facilitates enzyme crystal soaking with a ligand analog. Article de journal
Dans: J Appl Cryst, vol. 42, p. 279-283, 2009, ISBN: 10.1107/S0021889809003446.
Résumé | Liens | BibTeX | Étiquettes: Crystallization Agarose gel Ligands Inhibitors Soaking, FRUGIER, SAUTER, Unité ARN
@article{,
title = {Agarose gel facilitates enzyme crystal soaking with a ligand analog.},
author = {C Sauter and C Balg and A Moreno and K Dhouib and A Théobald-Dietrich and R Chenevert and R Giege and B Lorber},
url = {http://scripts.iucr.org/cgi-bin/paper?he5431},
isbn = {10.1107/S0021889809003446},
year = {2009},
date = {2009-01-01},
journal = {J Appl Cryst},
volume = {42},
pages = {279-283},
abstract = {Orthorhombic crystals of the enzyme aspartyl-tRNA synthetase (AspRS) were prepared in agarose gel, a chemical alternative to microgravity or nano-volume drops. Besides providing a convection-free medium, the network of the polysaccharide improved the stability of the crystalline lattice during soaking with L-aspartol adenylate, a synthetic and non-hydrolysable analog of the catalytic intermediate aspartyl adenylate. When crystals were embedded in the polysaccharide matrix the ligand reached their surfaces more uniformly. Gel-grown crystals exhibited well defined reflections even at high resolution and low mosaicity values, despite their fairly high solvent content and the relatively harsh flash cooling procedure. By contrast, soaked AspRS crystals prepared in solution broke apart within 10-30 s after the ligand was introduced into the mother liquor, and subsequently these fragments became an amorphous precipitate. A general objection to the use of gels in protein crystallization is that chemical interactions may occur between the polysaccharide matrix and proteins or ligands. The example of AspRS shows that this is not a major concern. This method may be generally applicable to crystal soaking with other small molecules or heavy atoms.},
keywords = {Crystallization Agarose gel Ligands Inhibitors Soaking, FRUGIER, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Lorber B, Sauter C, Théobald-Dietrich A, Moreno A, Schellenberger P, Robert M C, Capelle B, Sanglier S, Potier N, Giege R
Crystal growth of proteins, nucleic acids, and viruses in gels Article de journal
Dans: Prog Biophys Mol Biol, vol. 101, no. 1-3, p. 13-25, 2009, ISBN: 20005247, (1873-1732 (Electronic) 0079-6107 (Linking) Journal article).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, SAUTER, Unité ARN
@article{,
title = {Crystal growth of proteins, nucleic acids, and viruses in gels},
author = {B Lorber and C Sauter and A Théobald-Dietrich and A Moreno and P Schellenberger and M C Robert and B Capelle and S Sanglier and N Potier and R Giege},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20005247},
isbn = {20005247},
year = {2009},
date = {2009-01-01},
journal = {Prog Biophys Mol Biol},
volume = {101},
number = {1-3},
pages = {13-25},
abstract = {Medium-sized single crystals with perfect habits and no defect producing intense and well-resolved diffraction patterns are the dream of every protein crystallographer. Crystals of biological macromolecules possessing these characteristics can be prepared within a medium in which mass transport is restricted to diffusion. Chemical gels (like polysiloxane) and physical gels (such as agarose) provide such an environment and are therefore suitable for the crystallisation of biological macromolecules. Instructions for the preparation of each type of gel are given to urge crystal growers to apply diffusive media for enhancing crystallographic quality of their crystals. Examples of quality enhancement achieved with silica and agarose gels are given. Results obtained with other substances forming gel-like media (such as lipidic phases and cellulose derivatives) are presented. Finally, the use of gels in combination with capillary tubes for counter-diffusion experiments is discussed. Methods and techniques implemented with proteins can also be applied to nucleic acids and nucleoprotein assemblies such as viruses.},
note = {1873-1732 (Electronic)
0079-6107 (Linking)
Journal article},
keywords = {FRUGIER, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Dhouib K, Malek C Khan, Pfleging W, Gauthier-Manuel B, Duffait R, Thuillier G, Ferrigno R, Jacquamet L, Ohana J, Ferrer J L, Théobald-Dietrich A, Giege R, Lorber B, Sauter C
Microfluidic chips for the crystallization of biomacromolecules by counter-diffusion and on-chip crystal X-ray analysis Article de journal
Dans: Lab Chip, vol. 9, no. 10, p. 1412-1421, 2009, ISBN: 19417908, (1473-0197 (Print) 1473-0189 (Linking) Journal Article Research Support, Non-U.S. Gov't).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, SAUTER, Unité ARN, X-Ray/*instrumentation Dimethylpolysiloxanes/chemistry Macromolecular Substances/*chemistry Microfluidic Analytical Techniques/*instrumentation Polymethyl Methacrylate/chemistry
@article{,
title = {Microfluidic chips for the crystallization of biomacromolecules by counter-diffusion and on-chip crystal X-ray analysis},
author = {K Dhouib and C Khan Malek and W Pfleging and B Gauthier-Manuel and R Duffait and G Thuillier and R Ferrigno and L Jacquamet and J Ohana and J L Ferrer and A Théobald-Dietrich and R Giege and B Lorber and C Sauter},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19417908},
isbn = {19417908},
year = {2009},
date = {2009-01-01},
journal = {Lab Chip},
volume = {9},
number = {10},
pages = {1412-1421},
abstract = {Microfluidic devices were designed to perform on micromoles of biological macromolecules and viruses the search and the optimization of crystallization conditions by counter-diffusion, as well as the on-chip analysis of crystals by X-ray diffraction. Chips composed of microchannels were fabricated in poly-dimethylsiloxane (PDMS), poly-methyl-methacrylate (PMMA) and cyclo-olefin-copolymer (COC) by three distinct methods, namely replica casting, laser ablation and hot embossing. The geometry of the channels was chosen to ensure that crystallization occurs in a convection-free environment. The transparency of the materials is compatible with crystal growth monitoring by optical microscopy. The quality of the protein 3D structures derived from on-chip crystal analysis by X-ray diffraction using a synchrotron radiation was used to identify the most appropriate polymers. Altogether the results demonstrate that for a novel biomolecule, all steps from the initial search of crystallization conditions to X-ray diffraction data collection for 3D structure determination can be performed in a single chip.},
note = {1473-0197 (Print)
1473-0189 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {FRUGIER, SAUTER, Unité ARN, X-Ray/*instrumentation Dimethylpolysiloxanes/chemistry Macromolecular Substances/*chemistry Microfluidic Analytical Techniques/*instrumentation Polymethyl Methacrylate/chemistry},
pubstate = {published},
tppubtype = {article}
}
Messmer M, Putz J, Suzuki T, Sauter C, Sissler M, Florentz C
Tertiary network in mammalian mitochondrial tRNAAsp revealed by solution probing and phylogeny Article de journal
Dans: Nucleic Acids Res, vol. 37, no. 20, p. 6881-6895, 2009, ISBN: 19767615, (1362-4962 (Electronic) 0305-1048 (Linking) Journal Article Research Support, Non-U.S. Gov't).
Résumé | Liens | BibTeX | Étiquettes: Asp/*chemistry/*metabolism Transcription, Base Sequence Databases, FLORENTZ, FRUGIER, Genetic, Nucleic Acid Humans Molecular Sequence Data Nucleic Acid Conformation Phylogeny RNA/*chemistry/*metabolism RNA, SAUTER, SISSLER, Transfer, Unité ARN
@article{,
title = {Tertiary network in mammalian mitochondrial tRNAAsp revealed by solution probing and phylogeny},
author = {M Messmer and J Putz and T Suzuki and C Sauter and M Sissler and C Florentz},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19767615},
isbn = {19767615},
year = {2009},
date = {2009-01-01},
journal = {Nucleic Acids Res},
volume = {37},
number = {20},
pages = {6881-6895},
abstract = {Primary and secondary structures of mammalian mitochondrial (mt) tRNAs are divergent from canonical tRNA structures due to highly skewed nucleotide content and large size variability of D- and T-loops. The nonconservation of nucleotides involved in the expected network of tertiary interactions calls into question the rules governing a functional L-shaped three-dimensional (3D) structure. Here, we report the solution structure of human mt-tRNA(Asp) in its native post-transcriptionally modified form and as an in vitro transcript. Probing performed with nuclease S1, ribonuclease V1, dimethylsulfate, diethylpyrocarbonate and lead, revealed several secondary structures for the in vitro transcribed mt-tRNA(Asp) including predominantly the cloverleaf. On the contrary, the native tRNA(Asp) folds into a single cloverleaf structure, highlighting the contribution of the four newly identified post-transcriptional modifications to correct folding. Reactivities of nucleotides and phosphodiester bonds in the native tRNA favor existence of a full set of six classical tertiary interactions between the D-domain and the variable region, forming the core of the 3D structure. Reactivities of D- and T-loop nucleotides support an absence of interactions between these domains. According to multiple sequence alignments and search for conservation of Leontis-Westhof interactions, the tertiary network core building rules apply to all tRNA(Asp) from mammalian mitochondria.},
note = {1362-4962 (Electronic)
0305-1048 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {Asp/*chemistry/*metabolism Transcription, Base Sequence Databases, FLORENTZ, FRUGIER, Genetic, Nucleic Acid Humans Molecular Sequence Data Nucleic Acid Conformation Phylogeny RNA/*chemistry/*metabolism RNA, SAUTER, SISSLER, Transfer, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2008
Ryckelynck M, Paulus C A, Frugier M
Post-Translational Modifications Guard Yeast from Misaspartylation Article de journal
Dans: Biochemistry, vol. 47, no. 47, p. 12476-12482, 2008, ISBN: 18956891, (1520-4995 (Electronic) 0006-2960 (Linking) Journal article).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{,
title = {Post-Translational Modifications Guard Yeast from Misaspartylation},
author = {M Ryckelynck and C A Paulus and M Frugier},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18956885},
isbn = {18956891},
year = {2008},
date = {2008-01-01},
journal = {Biochemistry},
volume = {47},
number = {47},
pages = {12476-12482},
abstract = {Yeast aspartyl-tRNA synthetase (AspRS) is downregulated at the post-transcriptional level. This complex retro-inhibition mechanism causes the cell to equilibrate cellular concentrations of tRNA (Asp), AspRS, and its encoding mRNA. This strategy hinders AspRS accumulation to keep misacylation of heterologous tRNAs under control. Here, the AspRS concentration was increased artificially in vivo but did not generate tRNA (Asn) and/or tRNA (Glu) misaspartylation or the logical consecutive post-translational stress. This work allowed the detection of an additional subtle cellular lock capable of blocking AspRS toxicity. This study revealed the presence of post-translational modifications in the N-terminal extension of AspRS. We hypothesize that by neutralizing the lysine-rich motif contained in this domain, the cell mobilizes an additional strategy that considerably reduces the probability of the enzyme binding and aspartylating noncognate tRNAs and thus harming its own translation.},
note = {1520-4995 (Electronic)
0006-2960 (Linking)
Journal article},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Bonnefond L, Florentz C, Giege R, Rudinger-Thirion J
Decreased aminoacylation in pathology-related mutants of mitochondrial tRNATyr is associated with structural perturbations in tRNA architecture Article de journal
Dans: RNA, vol. 14, no. 4, p. 641-648, 2008, ISBN: 18268021, (1469-9001 (Electronic) In Vitro Journal Article Research Support, Non-U.S. Gov't).
Résumé | Liens | BibTeX | Étiquettes: Base Sequence Humans Mitochondrial Diseases/genetics/metabolism Models, FLORENTZ, FRUGIER, Molecular Molecular Sequence Data Nucleic Acid Conformation *Point Mutation RNA/*chemistry/*genetics/metabolism RNA Stability RNA, Transfer, Tyr/*chemistry/*genetics/metabolism *Transfer RNA Aminoacylation, Unité ARN
@article{,
title = {Decreased aminoacylation in pathology-related mutants of mitochondrial tRNATyr is associated with structural perturbations in tRNA architecture},
author = {L Bonnefond and C Florentz and R Giege and J Rudinger-Thirion},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18268021},
isbn = {18268021},
year = {2008},
date = {2008-01-01},
journal = {RNA},
volume = {14},
number = {4},
pages = {641-648},
abstract = {A growing number of human pathologies are ascribed to mutations in mitochondrial tRNA genes. Here, we report biochemical investigations on three mt-tRNA(Tyr) molecules with point substitutions associated with diseases. The mutations occur in the atypical T- and D-loops at positions homologous to those involved in the tertiary interaction network of canonical tRNAs. They do not correspond to tyrosine identity positions and likely do not contact the mitochondrial tyrosyl-tRNA synthetase during the aminoacylation process. The impact of these substitutions on mt-tRNA(Tyr) tyrosylation and structure was investigated using the corresponding tRNA transcripts. In vitro tyrosylation efficiency is decreased 600-fold for mutant A22G (mitochondrial gene mutation T5874C), 40-fold for G15A (C5877T), and is without significant effect on U54C (A5843G). Comparative solution probings with lead and nucleases on mutant and wild-type tRNA(Tyr) molecules reveal a greater sensitivity to single-strand specific probes for mutants G15A and A22G. For both transcripts, the mutation triggers a structural destabilization in the D-loop that propagates toward the anticodon arm and thus hinders efficient tyrosylation. Further probing analysis combined with phylogenetic data support the participation of G15 and A22 in the tertiary network of human mt-tRNA(Tyr) via nonclassical Watson-Crick G15-C48 and G13-A22 pairings. In contrast, the pathogenic effect of the tyrosylable mutant U54C, where structure is only marginally affected, has to be sought at another level of the tRNA(Tyr) life cycle.},
note = {1469-9001 (Electronic)
In Vitro
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {Base Sequence Humans Mitochondrial Diseases/genetics/metabolism Models, FLORENTZ, FRUGIER, Molecular Molecular Sequence Data Nucleic Acid Conformation *Point Mutation RNA/*chemistry/*genetics/metabolism RNA Stability RNA, Transfer, Tyr/*chemistry/*genetics/metabolism *Transfer RNA Aminoacylation, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Giege R, Touze E, Lorber B, Théobald-Dietrich A, Sauter C
Crystallogenesis trends of free and liganded aminoacyl-tRNA synthetases Article de journal
Dans: Crystal Growth & Design, vol. 8, no. 12, p. 4297-4306, 2008, ISBN: 10.1021/cg8007766.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, SAUTER, Unité ARN
@article{,
title = {Crystallogenesis trends of free and liganded aminoacyl-tRNA synthetases},
author = {R Giege and E Touze and B Lorber and A Théobald-Dietrich and C Sauter},
url = {http://pubs.acs.org/doi/abs/10.1021/cg8007766?prevSearch=%255BContrib%253A%2BSauter%2Bc%255D&searchHistoryKey=},
isbn = {10.1021/cg8007766},
year = {2008},
date = {2008-01-01},
journal = {Crystal Growth & Design},
volume = {8},
number = {12},
pages = {4297-4306},
abstract = {Aminoacyl-tRNA synthetases (aaRSs) catalyze the attachment of amino acids on transfer RNAs (tRNAs) and thus enable the correct expression of the genetic code during protein synthesis. After a brief historical review of early aaRS crystallizations we present results of a survey of the crystallization conditions of 220 aaRSs (either free or bound to small ligands) and of 59 aaRS:tRNA complexes whose structures are hosted by the RCSB Protein Data Bank. These structures at resolutions between 4.5 and 1.2 Å are those of synthetases from the three kingdoms of life. Their phylogenic distribution is heterogeneous: most stem from bacteria and archaea and some from eukarya and organelles. Interesting correlations are found between biochemical, physical−chemical, and crystallographic parameters. They highlight common and more specific features of the crystallogenesis of free or liganded aaRSs. The effects of the chemical nature of the crystallant(s), of ligands and other additives, as well as of the presence of impurities and of the presence of flexible polypeptide domains on protein or protein/RNA crystallization are examined. Features that favor the growth of crystals diffracting X-rays at high resolution are discussed.},
keywords = {FRUGIER, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2007
Touze E, Lorber B, Deniziak M, Becker H D, Kern D, Giege R, Sauter C
Disorder Can Exist inside Well-Diffracting Crystals Article de journal
Dans: Crystal Growth & Design, vol. 7, no. 11, p. 2195-2197, 2007, (DOI: 10.1021/cg7007057).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, GIEGE KERN FLORENTZ, SAUTER, Unité ARN
@article{,
title = {Disorder Can Exist inside Well-Diffracting Crystals},
author = {E Touze and B Lorber and M Deniziak and H D Becker and D Kern and R Giege and C Sauter},
url = {http://pubs.acs.org/doi/abs/10.1021/cg7007057?prevSearch=Touz%25C3%25A9&searchHistoryKey=},
year = {2007},
date = {2007-01-01},
journal = {Crystal Growth & Design},
volume = {7},
number = {11},
pages = {2195-2197},
abstract = {Unlike other glutaminyl-tRNA synthetases, the one from radioresistant bacterium Deinococcus radiodurans (Dr-GlnRS) possesses an additional C-terminal extension of 220 residues that shares some homology with the subunit of another enzyme of the translation machinery. Dr-GlnRS has been crystallized in an orthorhombic space group. The crystals diffract X-rays to a resolution of 2 Å. The determination of the structure of this atypical GlnRS showed that its N- and C-terminal appendices, which encompass in total one third of the proteinメs 852 amino acids, are actually disordered in the crystal lattice. This example demonstrates that macromolecule crystallization can tolerate large flexible regions in the solvent channels as long as they do not interfere with the packing contacts. This intriguing case is analyzed and discussed in light of current crystallogenesis strategies.},
note = {DOI: 10.1021/cg7007057},
keywords = {FRUGIER, GIEGE KERN FLORENTZ, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Sauter C, Dhouib K, Lorber B
From macrofluidies to microfluidies for the crystallization of biological macromolecules Article de journal
Dans: Crystal Growth & Design, vol. 7, no. 11, p. 2247-2250, 2007, (DOI: 10.1021/cg700955f).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, GIEGE FLORENTZ, SAUTER, Unité ARN
@article{,
title = {From macrofluidies to microfluidies for the crystallization of biological macromolecules},
author = {C Sauter and K Dhouib and B Lorber},
url = {http://pubs.acs.org/doi/abs/10.1021/cg700955f?prevSearch=sauter&searchHistoryKey=},
year = {2007},
date = {2007-01-01},
journal = {Crystal Growth & Design},
volume = {7},
number = {11},
pages = {2247-2250},
abstract = {This review presents the goals and principles of microfluidic technologies applied to the crystallization of biological macromolecules. A comparison of the devices that are available commercially or described in the literature summarizes the current state-of-the-art in microfluidics. A novel chip based on the counter-diffusion of solute molecules playing the role of crystallization agents is described. Inside the microfluidic channels composing the chip mass transport essentially occurs by diffusion. The chip is made of a rigid polymer that is impermeable to gases and compatible with crystal examination and monitoring in polarized light. The selected material is also transparent to X-rays, and three-dimensional protein structures can be determined from crystals contained inside this device using X-ray diffraction data collected on a synchrotron source. The outstanding quality of the electron-density maps demonstrates that on-chip crystal analysis is feasible. The replacement of conventional crystallization setups by inexpensive microfluidic chips for screening best crystallization agents and automated crystal diffraction analysis is discussed.},
note = {DOI: 10.1021/cg700955f},
keywords = {FRUGIER, GIEGE FLORENTZ, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2006
Jaeger S, Martin F, Rudinger-Thirion J, Giege R, Eriani G
Binding of human SLBP on the 3'-UTR of histone precursor H4-12 mRNA induces structural rearrangements that enable U7 snRNA anchoring Article de journal
Dans: Nucleic Acids Res, vol. 34, no. 17, p. 4987-4995, 2006, ISBN: 16982637, (1362-4962 (Electronic) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: ERIANI, FRUGIER, Unité ARN
@article{,
title = {Binding of human SLBP on the 3'-UTR of histone precursor H4-12 mRNA induces structural rearrangements that enable U7 snRNA anchoring},
author = {S Jaeger and F Martin and J Rudinger-Thirion and R Giege and G Eriani},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16982637},
isbn = {16982637},
year = {2006},
date = {2006-01-01},
journal = {Nucleic Acids Res},
volume = {34},
number = {17},
pages = {4987-4995},
abstract = {In metazoans, cell-cycle-dependent histones are produced from poly(A)-lacking mRNAs. The 3' end of histone mRNAs is formed by an endonucleolytic cleavage of longer precursors between a conserved stem-loop structure and a purine-rich histone downstream element (HDE). The cleavage requires at least two trans-acting factors: the stem-loop binding protein (SLBP), which binds to the stem-loop and the U7 snRNP, which anchors to histone pre-mRNAs by annealing to the HDE. Using RNA structure-probing techniques, we determined the secondary structure of the 3'-untranslated region (3'-UTR) of mouse histone pre-mRNAs H4-12, H1t and H2a-614. Surprisingly, the HDE is embedded in hairpin structures and is therefore not easily accessible for U7 snRNP anchoring. Probing of the 3'-UTR in complex with SLBP revealed structural rearrangements leading to an overall opening of the structure especially at the level of the HDE. Electrophoretic mobility shift assays demonstrated that the SLBP-induced opening of HDE actually facilitates U7 snRNA anchoring on the histone H4-12 pre-mRNAs 3' end. These results suggest that initial binding of the SLBP functions in making the HDE more accessible for U7 snRNA anchoring.},
note = {1362-4962 (Electronic)
Journal Article},
keywords = {ERIANI, FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Sauter C, Lorber B, Théobald-Dietrich A, Giege R, Khan-Malek C, Gauthier-Manuel B, Thuillier G, Ferrigno R
Dispositif microfluidique pour la cristallisation et l'analyse cristallographique de molécules. Divers
2006, ISBN: EP 2040809 A2.
BibTeX | Étiquettes: FRUGIER, GIEGE, SAUTER, Unité ARN
@misc{,
title = {Dispositif microfluidique pour la cristallisation et l'analyse cristallographique de molécules.},
author = {C Sauter and B Lorber and A Théobald-Dietrich and R Giege and C Khan-Malek and B Gauthier-Manuel and G Thuillier and R Ferrigno},
isbn = {EP 2040809 A2},
year = {2006},
date = {2006-01-01},
keywords = {FRUGIER, GIEGE, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {misc}
}
Rudinger-Thirion J, Olsthoorn R C, Giege R, Barends S
Idiosyncratic behaviour of tRNA-like structures in translation of plant Viral RNA genomes Article de journal
Dans: J Mol Biol, vol. 355, no. 5, p. 873-878, 2006, ISBN: 16337653, (0022-2836 (Print) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{,
title = {Idiosyncratic behaviour of tRNA-like structures in translation of plant Viral RNA genomes},
author = {J Rudinger-Thirion and R C Olsthoorn and R Giege and S Barends},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16337653},
isbn = {16337653},
year = {2006},
date = {2006-01-01},
journal = {J Mol Biol},
volume = {355},
number = {5},
pages = {873-878},
abstract = {Tobacco mosaic virus (TMV) and Nemesia ring necrosis virus (NeRNV) belong to the Tobamoviridae and Tymoviridae families, respectively. Although their RNAs present different 5'-untranslated regions and different family-specific genomic organizations, they share common 3'-ends organized into three consecutive pseudoknot structures followed by a histidylatable tRNA-like structure (TLS). We investigate here whether the histidine residue becomes incorporated into viral proteins and if the TLSs of TMV and NeRNV play a role in viral translation. Our results indicate that, regardless of the genomic context, the histidine moiety does not become incorporated in proteins via ribosomal translation, and that disruption of the TLS in either viral RNA does not perturb the viral translation patterns. In the light of the present data and of previous results on tymoviral TLS(Val) and bromoviral TLS(Tyr) showing differential effects on translation, we suggest that the key role for the TLS in promoting translation initiation appears to be dictated by the TLS architecture and identity.},
note = {0022-2836 (Print)
Journal Article},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Fender A, Sauter C, Messmer M, Putz J, Giege R, Florentz C, Sissler M
Loss of a primordial identity element for a mammalian mitochondrial aminoacylation system Article de journal
Dans: J Biol Chem, vol. 281, no. 23, p. 15980-15986, 2006, ISBN: 16597625, (0021-9258 (Print) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: Acylation Base Sequence Humans Kinetics Mutagenesis Nucleic Acid Conformation Plasmids RNA | Non-U.S. Gov't, Asp/chemistry/genetics/*metabolism Research Support, FLORENTZ, FRUGIER, Non-U.S. Gov't, SAUTER, SISSLER, Transfer, Unité ARN
@article{,
title = {Loss of a primordial identity element for a mammalian mitochondrial aminoacylation system},
author = {A Fender and C Sauter and M Messmer and J Putz and R Giege and C Florentz and M Sissler},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16597625},
isbn = {16597625},
year = {2006},
date = {2006-01-01},
journal = {J Biol Chem},
volume = {281},
number = {23},
pages = {15980-15986},
abstract = {In mammalian mitochondria the translational machinery is of dual origin with tRNAs encoded by a simplified and rapidly evolving mitochondrial (mt) genome and aminoacyl-tRNA synthetases (aaRS) coded by the nuclear genome, and imported. Mt-tRNAs are atypical with biased sequences, size variations in loops and stems, and absence of residues forming classical tertiary interactions, whereas synthetases appear typical. This raises questions about identity elements in mt-tRNAs and adaptation of their cognate mt-aaRSs. We have explored here the human mt-aspartate system in which a prokaryotic-type AspRS, highly similar to the Escherichia coli enzyme, recognizes a bizarre tRNA(Asp). Analysis of human mt-tRNA(Asp) transcripts confirms the identity role of the GUC anticodon as in other aspartylation systems but reveals the non-involvement of position 73. This position is otherwise known as the site of a universally conserved major aspartate identity element, G73, also known as a primordial identity signal. In mt-tRNA(Asp), position 73 can be occupied by any of the four nucleotides without affecting aspartylation. Sequence alignments of various AspRSs allowed placing Gly-269 at a position occupied by Asp-220, the residue contacting G73 in the crystallographic structure of E. coli AspRS-tRNA(Asp) complex. Replacing this glycine by an aspartate renders human mt-AspRS more discriminative to G73. Restriction in the aspartylation identity set, driven by a rapid mutagenic rate of the mt-genome, suggests a reverse evolution of the mt-tRNA(Asp) identity elements in regard to its bacterial ancestor.},
note = {0021-9258 (Print)
Journal Article},
keywords = {Acylation Base Sequence Humans Kinetics Mutagenesis Nucleic Acid Conformation Plasmids RNA | Non-U.S. Gov't, Asp/chemistry/genetics/*metabolism Research Support, FLORENTZ, FRUGIER, Non-U.S. Gov't, SAUTER, SISSLER, Transfer, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2005
Ryckelynck M, Masquida B, Giege R, Frugier M
An intricate RNA structure with two tRNA-derived motifs directs complex formation between yeast aspartyl-tRNA synthetase and its mRNA Article de journal
Dans: J Mol Biol, vol. 354, no. 3, p. 614-629, 2005, ISBN: 16257416, (0022-2836 (Print) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: Aspartate-tRNA Ligase/genetics/*metabolism Base Sequence DNA Footprinting Gene Deletion Models, FRUGIER, Messenger/*chemistry/*metabolism RNA, Molecular Molecular Sequence Data Nucleic Acid Conformation Protein Structure, Non-U.S. Gov't Saccharomyces cerevisiae/*enzymology/*genetics Sequence Alignment Sequence Homology, Nucleic Acid Solubility, Tertiary RNA, Transfer/*chemistry/*metabolism Research Support, Unité ARN
@article{,
title = {An intricate RNA structure with two tRNA-derived motifs directs complex formation between yeast aspartyl-tRNA synthetase and its mRNA},
author = {M Ryckelynck and B Masquida and R Giege and M Frugier},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16257416},
isbn = {16257416},
year = {2005},
date = {2005-01-01},
journal = {J Mol Biol},
volume = {354},
number = {3},
pages = {614-629},
abstract = {Accurate translation of genetic information necessitates the tuned expression of a large group of genes. Amongst them, controlled expression of the enzymes catalyzing the aminoacylation of tRNAs, the aminoacyl-tRNA synthetases, is essential to insure translational fidelity. In the yeast Saccharomyces cerevisiae, expression of aspartyl-tRNA synthetase (AspRS) is regulated in a process necessitating recognition of the 5' extremity of AspRS messenger RNA (mRNA(AspRS)) by its translation product and adaptation to the cellular tRNA(Asp) concentration. Here, we have established the folding of the approximately 300 nucleotides long 5' end of mRNA(AspRS) and identified the structural signals involved in the regulation process. We show that the regulatory region in mRNA(AspRS) folds in two independent and symmetrically structured domains spaced by two single-stranded connectors. Domain I displays a tRNA(Asp) anticodon-like stem-loop structure with mimics of the aspartate identity determinants, that is restricted in domain II to a short double-stranded helix. The overall mRNA structure, based on enzymatic and chemical probing, supports a three-dimensional model where each monomer of yeast AspRS binds one individual domain and recognizes the mRNA structure as it recognizes its cognate tRNA(Asp). Sequence comparison of yeast genomes shows that the features within the mRNA recognized by AspRS are conserved in different Saccharomyces species. In the recognition process, the N-terminal extension of each AspRS subunit plays a crucial role in anchoring the tRNA-like motifs of the mRNA on the synthetase.},
note = {0022-2836 (Print)
Journal Article},
keywords = {Aspartate-tRNA Ligase/genetics/*metabolism Base Sequence DNA Footprinting Gene Deletion Models, FRUGIER, Messenger/*chemistry/*metabolism RNA, Molecular Molecular Sequence Data Nucleic Acid Conformation Protein Structure, Non-U.S. Gov't Saccharomyces cerevisiae/*enzymology/*genetics Sequence Alignment Sequence Homology, Nucleic Acid Solubility, Tertiary RNA, Transfer/*chemistry/*metabolism Research Support, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Ryckelynck M, Giege R, Frugier M
tRNAs and tRNA mimics as cornerstones of aminoacyl-tRNA synthetase regulations Article de journal
Dans: Biochimie, vol. 87, no. 9-10, p. 835-845, 2005, ISBN: 15925436, (0300-9084 Journal article).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{,
title = {tRNAs and tRNA mimics as cornerstones of aminoacyl-tRNA synthetase regulations},
author = {M Ryckelynck and R Giege and M Frugier},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15925436},
isbn = {15925436},
year = {2005},
date = {2005-01-01},
journal = {Biochimie},
volume = {87},
number = {9-10},
pages = {835-845},
abstract = {Structural plasticity of transfer RNA (tRNA) molecules is essential for interactions with their biological partners in aminoacylation reactions and during ribosome-dependent protein synthesis. This holds true when tRNAs are recruited for other functions than translation. Here we review regulation pathways where tRNAs and tRNA mimics play a pivotal role. We further discuss the importance of the identity signals used in aminoacylation that are also required to specify regulatory mechanisms. Such mechanisms are diverse and intervene in transcription, splicing and translation. Altogether, the review highlights the many manners architectural features of tRNA were selected by evolution to control biological key processes.},
note = {0300-9084
Journal article},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Frugier M, Ryckelynck M, Giege R
tRNA-balanced expression of a eukaryal aminoacyl-tRNA synthetase by an mRNA-mediated pathway Article de journal
Dans: EMBO Rep, vol. 6, no. 9, p. 860-865, 2005, ISBN: 16113655, (1469-221x Journal article).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{,
title = {tRNA-balanced expression of a eukaryal aminoacyl-tRNA synthetase by an mRNA-mediated pathway},
author = {M Frugier and M Ryckelynck and R Giege},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16113655},
isbn = {16113655},
year = {2005},
date = {2005-01-01},
journal = {EMBO Rep},
volume = {6},
number = {9},
pages = {860-865},
abstract = {Aminoacylation of transfer RNAs is a key step during translation. It is catalysed by the aminoacyl-tRNA synthetases (aaRSs) and requires the specific recognition of their cognate substrates, one or several tRNAs, ATP and the amino acid. Whereas the control of certain aaRS genes is well known in prokaryotes, little is known about the regulation of eukaryotic aaRS genes. Here, it is shown that expression of AspRS is regulated in yeast by a feedback mechanism that necessitates the binding of AspRS to its messenger RNA. This regulation leads to a synchronized expression of AspRS and tRNA(Asp). The correlation between AspRS expression and mRNA(AspRS) and tRNA(Asp) concentrations, as well as the presence of AspRS in the nucleus, suggests an original regulation mechanism. It is proposed that the surplus of AspRS, not sequestered by tRNA(Asp), is imported into the nucleus where it binds to mRNA(AspRS) and thus inhibits its accumulation.},
note = {1469-221x
Journal article},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Bonnefond L, Frugier M, Giege R, Rudinger-Thirion J
Human mitochondrial TyrRS disobeys the tyrosine identity rules Article de journal
Dans: RNA, vol. 11, no. 5, p. 558-562, 2005, ISBN: 15840810, (1355-8382 Journal Article).
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence Base Sequence Catalytic Domain Humans Mitochondria/*enzymology Molecular Sequence Data RNA, FRUGIER, Non-U.S. Gov't Substrate Specificity Tyrosine/genetics/*metabolism Tyrosine-tRNA Ligase/chemistry/*metabolism, Transfer, Tyr/genetics/*metabolism Research Support, Unité ARN
@article{,
title = {Human mitochondrial TyrRS disobeys the tyrosine identity rules},
author = {L Bonnefond and M Frugier and R Giege and J Rudinger-Thirion},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15840810},
isbn = {15840810},
year = {2005},
date = {2005-01-01},
journal = {RNA},
volume = {11},
number = {5},
pages = {558-562},
abstract = {Human tyrosyl-tRNA synthetase from mitochondria (mt-TyrRS) presents dual sequence features characteristic of eubacterial and archaeal TyrRSs, especially in the region containing amino acids recognizing the N1-N72 tyrosine identity pair. This would imply that human mt-TyrRS has lost the capacity to discriminate between the G1-C72 pair typical of eubacterial and mitochondrial tRNATyr and the reverse pair C1-G72 present in archaeal and eukaryal tRNATyr. This expectation was verified by a functional analysis of wild-type or mutated tRNATyr molecules, showing that mt-TyrRS aminoacylates with similar catalytic efficiency its cognate tRNATyr with G1-C72 and its mutated version with C1-G72. This provides the first example of a TyrRS lacking specificity toward N1-N72 and thus of a TyrRS disobeying the identity rules. Sequence comparisons of mt-TyrRSs across phylogeny suggest that the functional behavior of the human mt-TyrRS is conserved among all vertebrate mt-TyrRSs.},
note = {1355-8382
Journal Article},
keywords = {Amino Acid Sequence Base Sequence Catalytic Domain Humans Mitochondria/*enzymology Molecular Sequence Data RNA, FRUGIER, Non-U.S. Gov't Substrate Specificity Tyrosine/genetics/*metabolism Tyrosine-tRNA Ligase/chemistry/*metabolism, Transfer, Tyr/genetics/*metabolism Research Support, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Ambrogelly A, Frugier M, Ibba M, Soll D, Giege R
Transfer RNA recognition by class I lysyl-tRNA synthetase from the Lyme disease pathogen Borrelia burgdorferi Article de journal
Dans: FEBS Lett, vol. 579, no. 12, p. 2629-2634, 2005, ISBN: 15862301, (0014-5793 Journal Article).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{,
title = {Transfer RNA recognition by class I lysyl-tRNA synthetase from the Lyme disease pathogen Borrelia burgdorferi},
author = {A Ambrogelly and M Frugier and M Ibba and D Soll and R Giege},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15862301},
isbn = {15862301},
year = {2005},
date = {2005-01-01},
journal = {FEBS Lett},
volume = {579},
number = {12},
pages = {2629-2634},
abstract = {Borrelia burgdorferi and other spirochetes contain a class I lysyl-tRNA synthetase (LysRS), in contrast to most eubacteria that have a canonical class II LysRS. We analyzed tRNA(Lys) recognition by B. burgdorferi LysRS, using two complementary approaches. First, the nucleotides of B. burgdorferi tRNA(Lys) in contact with B. burgdorferi LysRS were determined by enzymatic footprinting experiments. Second, the kinetic parameters for a series of variants of the B. burgdorferi tRNA(Lys) were then determined during aminoacylation by B. burgdorferi LysRS. The identity elements were found to be mostly located in the anticodon and in the acceptor stem. Transplantation of the identified identity elements into the Escherichia coli tRNA(Asp) scaffold endowed lysylation activity on the resulting chimera, indicating that a functional B. burgdorferi lysine tRNA identity set had been determined.},
note = {0014-5793
Journal Article},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Biertümpfel C, Basquin J, Birkenbihl R, Suck D, Sauter C
Characterization of crystals of the Hjc resolvase from Archaeoglobus fulgidus grown in gel by counter-diffusion. Article de journal
Dans: Acta Crystallogr F Struct Biol Commun, vol. 61, no. 7, p. 684-687, 2005.
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, GIEGE Holliday junction-cutting enzyme Hjc Resolvase Counter-duffusion Agarose gel, SAUTER, Unité ARN
@article{,
title = {Characterization of crystals of the Hjc resolvase from Archaeoglobus fulgidus grown in gel by counter-diffusion.},
author = {C Biertümpfel and J Basquin and R Birkenbihl and D Suck and C Sauter},
url = {http://scripts.iucr.org/cgi-bin/paper?za5109},
doi = {10.1107/S1744309105018269},
year = {2005},
date = {2005-01-01},
journal = {Acta Crystallogr F Struct Biol Commun},
volume = {61},
number = {7},
pages = {684-687},
abstract = {Holliday junction-resolving enzymes are ubiquitous proteins that play a key role in DNA repair and reorganization by homologous recombination. The Holliday junction-cutting enzyme (Hjc) from the archaeon Archaeoglobus fulgidus is a member of this group. The first Hjc crystals were obtained by conventional sparse-matrix screening. They exhibited an unusually elongated unit cell and their X-ray characterization required special care to avoid spot overlaps along the c* axis. The use of an arc appended to the goniometric head allowed proper orientatation of plate-like crystals grown in agarose gel by counter-diffusion. Thus, complete diffraction data were collected at 2.7 Å resolution using synchrotron radiation. They belong to space group P3121 or P3221, with unit-cell parameters a = b = 37.4},
keywords = {FRUGIER, GIEGE Holliday junction-cutting enzyme Hjc Resolvase Counter-duffusion Agarose gel, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Moreno A, Théobald-Dietrich A, Lorber B, Sauter C, Giege R
Effects of macromolecular impurities and of crystallization method on the quality of eubacterial aspartyl-tRNA synthetase crystals Article de journal
Dans: Acta Crystallogr D Biol Crystallogr, vol. 61, no. Pt 6, p. 789-792, 2005, ISBN: 15930641, (0907-4449 Journal Article).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, SAUTER, Unité ARN
@article{,
title = {Effects of macromolecular impurities and of crystallization method on the quality of eubacterial aspartyl-tRNA synthetase crystals},
author = {A Moreno and A Théobald-Dietrich and B Lorber and C Sauter and R Giege},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15930641},
isbn = {15930641},
year = {2005},
date = {2005-01-01},
journal = {Acta Crystallogr D Biol Crystallogr},
volume = {61},
number = {Pt 6},
pages = {789-792},
abstract = {Although macromolecular purity is thought to be essential for the growth of flawless protein crystals, only a few studies have investigated how contaminants alter the crystallization process and crystal quality. Likewise, the outcome of a crystallization process may vary with the crystallization method. Here, it is reported how these two variables affect the crystallogenesis of aspartyl-tRNA synthetase from the eubacterium Thermus thermophilus. This homodimeric enzyme (Mr=130,000) possesses a multi-domain architecture and crystallizes either in a monoclinic or an orthorhombic habit. Minute amounts of protein impurities alter to a different extent the growth of each crystal form. The best synthetase crystals are only obtained when the crystallizing solution is either enclosed in capillaries or immobilized in agarose gel. In these two environments convection is reduced with regard to that existing in an unconstrained solution.},
note = {0907-4449
Journal Article},
keywords = {FRUGIER, SAUTER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Théobald-Dietrich A, Giege R, Rudinger-Thirion J
Evidence for the existence in mRNAs of a hairpin element responsible for ribosome dependent pyrrolysine insertion into proteins Article de journal
Dans: Biochimie, vol. 87, no. 9-10, p. 813-817, 2005, ISBN: 16164991, (0300-9084 Journal article).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{,
title = {Evidence for the existence in mRNAs of a hairpin element responsible for ribosome dependent pyrrolysine insertion into proteins},
author = {A Théobald-Dietrich and R Giege and J Rudinger-Thirion},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16164991},
isbn = {16164991},
year = {2005},
date = {2005-01-01},
journal = {Biochimie},
volume = {87},
number = {9-10},
pages = {813-817},
abstract = {In the methanogenic archae Methanosarcina barkeri, insertion of pyrrolysine, the 22nd amino acid, results from the decoding of an amber UAG codon in the mRNA of monomethylamine methyltransferases (MtmB). Sequence comparisons combined with structural enzymatic and chemical probing on M. barkeri MtmB1 mRNA demonstrate the presence of a hairpin motif located immediately after the redefined UAG codon. This structure of 86 nucleotides differs slightly from a proposal given in the literature and comprises four successive stems separated by three internal loops and closed by a large apical loop. Sequence alignments of MtmB mRNAs of different Methanosarcinacae reveal a conservation of the motif in both sequence and folding levels. The functional role of this motif as a signal leading to pyrrolysine insertion is discussed.},
note = {0300-9084
Journal article},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Bonnefond L, Giege R, Rudinger-Thirion J
Evolution of the tRNA(Tyr)/TyrRS aminoacylation systems Article de journal
Dans: Biochimie, vol. 87, no. 9-10, p. 873-883, 2005, ISBN: 16164994, (0300-9084 Journal Article).
Résumé | Liens | BibTeX | Étiquettes: FRUGIER, Unité ARN
@article{,
title = {Evolution of the tRNA(Tyr)/TyrRS aminoacylation systems},
author = {L Bonnefond and R Giege and J Rudinger-Thirion},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16164994},
isbn = {16164994},
year = {2005},
date = {2005-01-01},
journal = {Biochimie},
volume = {87},
number = {9-10},
pages = {873-883},
abstract = {The tRNA identity rules ensuring fidelity of translation are globally conserved throughout evolution except for tyrosyl-tRNA synthetases (TyrRSs) that display species-specific tRNA recognition. This discrimination originates from the presence of a conserved identity pair, G1-C72, located at the top of the acceptor stem of tRNA(Tyr) from eubacteria that is invariably replaced by an unusual C1-G72 pair in archaeal and eubacterial tRNA(Tyr). In addition to the key role of pair 1-72 in tyrosylation, discriminator base A73, the anticodon triplet and the large variable region (present in eubacterial tRNA(Tyr) but not found in eukaryal tRNA(Tyr)) contribute to tyrosylation with variable strengths. Crystallographic structures of two tRNA(Tyr)/TyrRS complexes revealed different interaction modes in accordance with the phylum-specificity. Recent functional studies on the human mitochondrial tRNA(Tyr)/TyrRS system indicates strong deviations from the canonical tyrosylation rules. These differences are discussed in the light of the present knowledge on TyrRSs.},
note = {0300-9084
Journal Article},
keywords = {FRUGIER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}