{"doi":"10.1016/j.jbc.2024.107756","title":"Murine nuclear tyrosyl-tRNA synthetase deficiency leads to fat storage deficiency and hearing loss","abstract":"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.","journal":"Journal of Biological Chemistry","year":2024,"id":503213,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":true,"deposit_databanks":{"SRA":["PRJNA1148973"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1352816,"name":"Jiadong Zhou","orcid":"0000-0001-6766-5865","position":1,"is_corresponding":false},{"id":324757,"name":"Jianjie Dong","orcid":null,"position":2,"is_corresponding":false},{"id":379648,"name":"Salvador Huitrón‐Reséndiz","orcid":null,"position":3,"is_corresponding":false},{"id":797195,"name":"Ely Cheikh Boussaty","orcid":"0000-0003-3146-8821","position":4,"is_corresponding":false},{"id":1353146,"name":"Eduardo Campos Chavez","orcid":null,"position":5,"is_corresponding":false},{"id":333692,"name":"Na Wei","orcid":"0000-0003-2093-3441","position":6,"is_corresponding":false},{"id":1096388,"name":"Calin Dan Dumitru","orcid":null,"position":7,"is_corresponding":false},{"id":575094,"name":"Yosuke Morodomi","orcid":"0000-0002-8882-0833","position":8,"is_corresponding":false},{"id":575097,"name":"Taisuke Kanaji","orcid":"0000-0002-3588-6038","position":9,"is_corresponding":false},{"id":326706,"name":"Allen F. Ryan","orcid":"0000-0001-9894-8083","position":10,"is_corresponding":false},{"id":780954,"name":"Rick A. Friedman","orcid":null,"position":11,"is_corresponding":false},{"id":400723,"name":"Tong Zhou","orcid":"0000-0001-9960-1073","position":12,"is_corresponding":false},{"id":149487,"name":"Sachiko Kanaji","orcid":null,"position":13,"is_corresponding":false},{"id":324887,"name":"Matthew Wortham","orcid":null,"position":14,"is_corresponding":false},{"id":235322,"name":"Simon Schenk","orcid":"0000-0002-8224-3203","position":15,"is_corresponding":false},{"id":262442,"name":"Amanda J. Roberts","orcid":"0000-0002-4044-8884","position":16,"is_corresponding":false},{"id":479459,"name":"Xiang‐Lei Yang","orcid":"0000-0003-2554-084X","position":17,"is_corresponding":false},{"id":1095978,"name":"Julia Jones","orcid":"0000-0001-9429-8925","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T02:10:27.781502Z","pmid":"39260699","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}