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The role of tRNA synthetases in neurological and neuromuscular disorders

Lookup NU author(s): Dr Veronika Boczonadi, Matt Jennings, Professor Rita Horvath

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes responsible for charging tRNAs with their cognate amino acids, therefore essential for the first step in protein synthesis. Although the majority of protein synthesis happens in the cytosol, an additional translation apparatus is required to translate the 13 mitochondrial DNA-encoded proteins important for oxidative phosphorylation. Most ARS genes in these cellular compartments are distinct, but two genes are common, encoding aminoacyl-tRNA synthetases of glycine (GARS) and lysine (KARS) in both mitochondria and the cytosol. Mutations in the majority of the 37 nuclear-encoded human ARS genes have been linked to a variety of recessive and dominant tissue-specific disorders. Current data indicate that impaired enzyme function could explain the pathogenicity, however not all pathogenic ARSs mutations result in deficient catalytic function; thus, the consequences of mutations may arise from other molecular mechanisms. The peripheral nerves are frequently affected, as illustrated by the high number of mutations in cytosolic and bifunctional tRNA synthetases causing Charcot–Marie–Tooth disease (CMT). Here we provide insights on the pathomechanisms of CMT-causing tRNA synthetases with specific focus on the two bifunctional tRNA synthetases (GARS, KARS).


Publication metadata

Author(s): Boczonadi V, Jennings MJ, Horvath R

Publication type: Article

Publication status: Published

Journal: FEBS letters

Year: 2018

Volume: 592

Issue: 5

Pages: 703-717

Print publication date: 01/03/2018

Online publication date: 01/02/2018

Acceptance date: 21/12/2017

ISSN (print): 0014-5793

ISSN (electronic): 1873-3468

Publisher: John Wiley & Sons Ltd.

URL: https://doi.org/10.1002/1873-3468.12962

DOI: 10.1002/1873-3468.12962


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