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Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria.

Hilander, T; Zhou, X-L; Konovalova, S; Zhang, F-P; Euro, L; Chilov, D; Poutanen, M; Chihade, J; Wang, E-D; Tyynismaa, H (2018) Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria. Nucleic Acids Res, 46 (2). pp. 849-860. ISSN 1362-4962 https://doi.org/10.1093/nar/gkx1231
SGUL Authors: Hilander, Taru

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Abstract

Accuracy of protein synthesis is enabled by the selection of amino acids for tRNA charging by aminoacyl-tRNA synthetases (ARSs), and further enhanced by the proofreading functions of some of these enzymes for eliminating tRNAs mischarged with noncognate amino acids. Mouse models of editing-defective cytoplasmic alanyl-tRNA synthetase (AlaRS) have previously demonstrated the importance of proofreading for cytoplasmic protein synthesis, with embryonic lethal and progressive neurodegeneration phenotypes. Mammalian mitochondria import their own set of nuclear-encoded ARSs for translating critical polypeptides of the oxidative phosphorylation system, but the importance of editing by the mitochondrial ARSs for mitochondrial proteostasis has not been known. We demonstrate here that the human mitochondrial AlaRS is capable of editing mischarged tRNAs in vitro, and that loss of the proofreading activity causes embryonic lethality in mice. These results indicate that tRNA proofreading is essential in mammalian mitochondria, and cannot be overcome by other quality control mechanisms.

Item Type: Article
Additional Information: © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Keywords: Developmental Biology, 05 Environmental Sciences, 06 Biological Sciences, 08 Information And Computing Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Nucleic Acids Res
ISSN: 1362-4962
Language: eng
Dates:
DateEvent
25 January 2018Published
8 December 2017Published Online
30 November 2017Accepted
Publisher License: Creative Commons: Attribution-Noncommercial 4.0
Projects:
Project IDFunderFunder ID
637458European Research Councilhttp://dx.doi.org/10.13039/501100000781
2017YFA0504000National Key Research and Development Program of ChinaUNSPECIFIED
31670801Natural Science Foundation of ChinaUNSPECIFIED
91440204Natural Science Foundation of ChinaUNSPECIFIED
6QA1404400Shanghai Rising-Star ProgramUNSPECIFIED
15ZR1446500Committee of Science and Technology in ShanghaiUNSPECIFIED
PubMed ID: 29228266
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109573
Publisher's version: https://doi.org/10.1093/nar/gkx1231

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