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. Not

SUBMITTER: Jones JA 

PROVIDER: S-EPMC11470617 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature