Murine nuclear tyrosyl-tRNA synthetase deficiency leads to fat storage deficiency and hearing loss.

Autor:	Jones JA; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA., Zhou J; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA., Dong J; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA., Huitron-Resendiz S; Animal Models Core Facility, The Scripps Research Institute, La Jolla, California, USA., Boussaty E; Department of Otolaryngology - Head and Neck Surgery, University of California San Diego, La Jolla, California, USA., Chavez E; Department of Otolaryngology - Head and Neck Surgery, University of California San Diego, La Jolla, California, USA., Wei N; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA., Dumitru CD; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA., Morodomi Y; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA., Kanaji T; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA., Ryan AF; Department of Otolaryngology - Head and Neck Surgery, University of California San Diego, La Jolla, California, USA., Friedman R; Department of Otolaryngology - Head and Neck Surgery, University of California San Diego, La Jolla, California, USA., Zhou T; Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA., Kanaji S; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA., Wortham M; Department of Pediatrics, Pediatric Diabetes Research Center, University of California San Diego, La Jolla, California, USA., Schenk S; Department of Orthopaedic Surgery, University of California San Diego, La Jolla, California, USA., Roberts AJ; Animal Models Core Facility, The Scripps Research Institute, La Jolla, California, USA., Yang XL; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA. Electronic address: xlyang@scripps.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Oct; Vol. 300 (10), pp. 107756. Date of Electronic Publication: 2024 Sep 12.
DOI:	10.1016/j.jbc.2024.107756
Abstrakt:	Aminoacyl-tRNA synthetases are fundamental to the translation machinery with emerging roles in transcriptional regulation. Previous cellular studies have demonstrated tyrosyl-tRNA synthetase (YARS1 or TyrRS) as a stress response protein through its cytosol-nucleus translocation to maintain cellular homeostasis. Here, we established a mouse model with a disrupted TyrRS nuclear localization signal, revealing its systemic impact on metabolism. Nuclear TyrRS deficiency (Yars ΔNLS ) led to reduced lean mass, reflecting a mild developmental defect, and reduced fat mass, possibly due to increased energy expenditure. Consistently, Yars ΔNLS mice exhibit improved insulin sensitivity and reduced insulin levels, yet maintain normoglycemia, indicative of enhanced insulin action. Notably, Yars ΔNLS mice also develop progressive hearing loss. These findings underscore the crucial function of nuclear TyrRS in the maintenance of fat storage and hearing and suggest that aminoacyl-tRNA synthetases' regulatory roles can affect metabolic pathways and tissue-specific health. This work broadens our understanding of how protein synthesis interconnects metabolic regulation to ensure energy efficiency. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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