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

• DOI: 10.1101/416727
• Publication Date: 2018-09-14T03:35:18Z
• Authors: Doowon Huh; Maria C. Passarelli; Jenny Gao; Shahnoza N Dusmatova; Clara Goin; Lisa Fish; Alexandra M. Pinzaru; Henrik Molina; Elizabeth A. McMi...; Hosseinali Asgharian; Hani Goodarzi; Sohail F. Tavazoie
• Keywords: Translational regulation; Fragmentation; Genetic Code

SUMMARY Eukaryotic transfer RNAs can become selectively fragmented upon various stresses, generating tRNA-derived small RNA fragments. Such fragmentation has been reported to impact a fraction of the tRNA pool and thus presumed not directly translation. We report that oxidative stress rapidly generate tyrosine GUA fragments in human cells—causing significant depletion precursor tRNA. Tyrosine impaired translation growth metabolic genes enriched cognate codons. Depletion or its translationally regulated targets USP3 SCD repressed proliferation—revealing dedicated tRNA-regulated suppressive pathway for response. are generated DIS3L2 exoribonuclease-dependent manner inhibit hnRNPA1-mediated transcript destabilization. Moreover, is conserved C. elegans . Thus, coordinately trans -acting small-RNAs functionally deplete Our findings reveal existence an underlying adaptive codon-based regulatory response inherent genetic code.