Nuclear translocation of an aminoacyl-tRNA synthetase may mediate a chronic "integrated stress response".

ABSTRACT: Various stress conditions are signaled through phosphorylation of translation initiation factor eukaryotic initiation factor 2α (eIF2α) to inhibit global translation while selectively activating transcription factor ATF4 to aid cell survival and recovery. However, this integrated stress response is acute and cannot resolve lasting stress. Here, we report that tyrosyl-tRNA synthetase (TyrRS), a member of the aminoacyl-tRNA synthetase family that responds to diverse stress conditions through cytosol-nucleus translocation to activate stress-response genes, also inhibits global translation. However, it occurs at a later stage than eIF2α/ATF4 and mammalian target of rapamycin (mTOR) responses. Excluding TyrRS from the nucleus over-activates translation and increases apoptosis in cells under pro

SUBMITTER: Jones JA 

PROVIDER: S-EPMC10592355 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature