Publications
2003
Levinger L, Giege R, Florentz C
Pathology-related substitutions in human mitochondrial tRNA(Ile) reduce precursor 3' end processing efficiency in vitro Article de journal
Dans: Nucleic Acids Res, vol. 31, no. 7, p. 1904-1912, 2003, ISBN: 12655007, (1362-4962 Journal Article).
Résumé | Liens | BibTeX | Étiquettes: Base Sequence DNA, FLORENTZ, Ile/*genetics/metabolism Support, Mitochondrial/*genetics Endoribonucleases/metabolism Hela Cells Human Kinetics Molecular Sequence Data Mutation RNA Precursors/genetics/metabolism *RNA Processing, Non-U.S. Gov't Support, P.H.S., Post-Transcriptional RNA, Transfer, U.S. Gov't, Unité ARN
@article{,
title = {Pathology-related substitutions in human mitochondrial tRNA(Ile) reduce precursor 3' end processing efficiency in vitro},
author = {L Levinger and R Giege and C Florentz},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12655007},
isbn = {12655007},
year = {2003},
date = {2003-01-01},
journal = {Nucleic Acids Res},
volume = {31},
number = {7},
pages = {1904-1912},
abstract = {The human mitochondrial genome encodes 22 tRNAs interspersed among the two rRNAs and 11 mRNAs, often without spacers, suggesting that tRNAs must be efficiently excised. Numerous maternally transmitted diseases and syndromes arise from mutations in mitochondrial tRNAs, likely due to defect(s) in tRNA metabolism. We have systematically explored the effect of pathogenic mutations on tRNA(Ile) precursor 3' end maturation in vitro by 3'-tRNase. Strikingly, four pathogenic tRNA(Ile) mutations reduce 3'-tRNase processing efficiency (V(max) / K(M)) to approximately 10-fold below that of wild-type, principally due to lower V(max). The structural impact of mutations was sought by secondary structure probing and wild-type tRNA(Ile) precursor was found to fold into a canonical cloverleaf. Among the mutant tRNA(Ile) precursors with the greatest 3' end processing deficiencies, only G4309A displays a secondary structure substantially different from wild-type, with changes in the T domain proximal to the substitution. Reduced efficiency of tRNA(Ile) precursor 3' end processing, in one case associated with structural perturbations, could thus contribute to human mitochondrial diseases caused by mutant tRNAs.},
note = {1362-4962
Journal Article},
keywords = {Base Sequence DNA, FLORENTZ, Ile/*genetics/metabolism Support, Mitochondrial/*genetics Endoribonucleases/metabolism Hela Cells Human Kinetics Molecular Sequence Data Mutation RNA Precursors/genetics/metabolism *RNA Processing, Non-U.S. Gov't Support, P.H.S., Post-Transcriptional RNA, Transfer, U.S. Gov't, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
The human mitochondrial genome encodes 22 tRNAs interspersed among the two rRNAs and 11 mRNAs, often without spacers, suggesting that tRNAs must be efficiently excised. Numerous maternally transmitted diseases and syndromes arise from mutations in mitochondrial tRNAs, likely due to defect(s) in tRNA metabolism. We have systematically explored the effect of pathogenic mutations on tRNA(Ile) precursor 3' end maturation in vitro by 3'-tRNase. Strikingly, four pathogenic tRNA(Ile) mutations reduce 3'-tRNase processing efficiency (V(max) / K(M)) to approximately 10-fold below that of wild-type, principally due to lower V(max). The structural impact of mutations was sought by secondary structure probing and wild-type tRNA(Ile) precursor was found to fold into a canonical cloverleaf. Among the mutant tRNA(Ile) precursors with the greatest 3' end processing deficiencies, only G4309A displays a secondary structure substantially different from wild-type, with changes in the T domain proximal to the substitution. Reduced efficiency of tRNA(Ile) precursor 3' end processing, in one case associated with structural perturbations, could thus contribute to human mitochondrial diseases caused by mutant tRNAs.