Document Type

Article

Publication Date

10-16-2023

Keywords

JMG

JAX Source

Annu Rev Cell Dev Biol. 2023;39:223-52.

ISSN

1530-8995

PMID

37339680

DOI

https://doi.org/10.1146/annurev-cellbio-021623-124009

Grant

Work in the Storkebaum Lab is supported by a European Research Council (ERC) consolida- tor grant (ERC-2017-COG 770244) and funding from the Radala Foundation, Stichting ALS Nederland, the French Muscular Dystrophy Association (AFM-Téléthon), Association pour la Recherche sur la Sclérose Latérale Amyotrophique (ARSLA), the Prinses Beatrix Spierfonds (W.OR22-03), the Muscular Dystrophy Association (MDA 946876), and a Dutch Research Coun- cil (NWO) Open Competition ENW-M grant. The Burgess Lab is supported by the National Institutes of Health, including grants R37NS054154 and R01NS113583, and the Paul E. Kelly Foundation. We would like to thank members of the Burgess Lab for comments on the manuscript and Zoe Reifsnyder at JAX Creative for assistance with the figures and table.

Abstract

Transfer RNAs (tRNAs) decode messenger RNA codons to peptides at the ribosome. The nuclear genome contains many tRNA genes for each amino acid and even each anticodon. Recent evidence indicates that expression of these tRNAs in neurons is regulated, and they are not functionally redundant. When specific tRNA genes are nonfunctional, this results in an imbalance between codon demand and tRNA availability. Furthermore, tRNAs are spliced, processed, and posttranscriptionally modified. Defects in these processes lead to neurological disorders. Finally, mutations in the aminoacyl tRNA synthetases (aaRSs) also lead to disease. Recessive mutations in several aaRSs cause syndromic disorders, while dominant mutations in a subset of aaRSs lead to peripheral neuropathy, again due to an imbalance between tRNA supply and codon demand. While it is clear that disrupting tRNA biology often leads to neurological disease, additional research is needed to understand the sensitivity of neurons to these changes.

Comments

Copyright © 2023 by the author(s). This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

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