A stress-induced tyrosine-tRNA depletion response mediates codon-based translational repression and growth suppression.

ABSTRACT: Eukaryotic transfer RNAs can become selectively fragmented upon various stresses, generating tRNA-derived small RNA fragments. Such fragmentation has been reported to impact a small fraction of the tRNA pool and thus presumed to not directly impact translation. We report that oxidative stress can rapidly generate tyrosine-tRNA_GUA fragments in human cells-causing significant depletion of the precursor tRNA. Tyrosine-tRNA_GUA depletion impaired translation of growth and metabolic genes enriched in cognate tyrosine codons. Depletion of tyrosine tRNA_GUA or its translationally regulated targets USP3 and SCD repressed proliferation-revealing a dedicated tRNA-regulated growth-suppressive pathway for oxidative stress response. Tyrosine fragments are generated in a D

SUBMITTER: Huh D 

PROVIDER: S-EPMC7809793 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature