Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria

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Hilander , T , Zhou , X-L , Konovalova , S , Zhang , F-P , Euro , L , Shilov , D , Poutanen , M , Chihade , J , Wang , E-D & Tyynismaa , H 2018 , ' Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria ' , Nucleic Acids Research , vol. 46 , no. 2 , pp. 849–860 . https://doi.org/10.1093/nar/gkx1231

Title: Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria
Author: Hilander, Taru; Zhou, Xiao-Long; Konovalova, Svetlana; Zhang, Fu-Ping; Euro, Liliya; Shilov, Dmitri; Poutanen, Matti; Chihade, Joseph; Wang, En-Duo; Tyynismaa, Henna
Contributor organization: Research Programme for Molecular Neurology
Henna Tyynismaa / Principal Investigator
Research Programs Unit
University of Helsinki
Medicum
Department of Medical and Clinical Genetics
Centre of Excellence in Stem Cell Metabolism
Date: 2018-01-25
Language: eng
Number of pages: 12
Belongs to series: Nucleic Acids Research
ISSN: 0305-1048
DOI: https://doi.org/10.1093/nar/gkx1231
URI: http://hdl.handle.net/10138/231582
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.
Subject: 3111 Biomedicine
QUALITY-CONTROL
HUMAN-DISEASE
SYNTHETASE MUTATIONS
PROTEIN-SYNTHESIS
AMINOACYLATION
DEFECTS
MISTRANSLATION
RECOGNITION
POLYMERASE
PROTEASES
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion


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