한빛사논문
- 조회657
Doowon Huh1, Maria C Passarelli1, Jenny Gao1, Shahnoza N Dusmatova1, Clara Goin1, Lisa Fish2, Alexandra M Pinzaru1, Henrik Molina3, Zhiji Ren1, Elizabeth A McMillan1, Hosseinali sgharian2, Hani Goodarzi2 and Sohail F Tavazoie*,1
1Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY, USA
2Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA, USA
3Proteome Resource Center, The Rockefeller University, New York, NY, USA
*Corresponding author.
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‐tRNAGUA fragments in human cells—causing significant depletion of the precursor tRNA. Tyrosine‐tRNAGUA depletion impaired translation of growth and metabolic genes enriched in cognate tyrosine codons. Depletion of tyrosine tRNAGUA 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 DIS3L2 exoribonuclease‐dependent manner and inhibit hnRNPA1‐mediated transcript destabilization. Moreover, tyrosine fragmentation is conserved in C. elegans. Thus, tRNA fragmentation can coordinately generate trans‐acting small RNAs and functionally deplete a tRNA. Our findings reveal the existence of an underlying adaptive codon‐based regulatory response inherent to the genetic code.
논문정보
- Research article
- 2020년 12월 (BRIC 등록일 2020-12-29)
- 국외 연구진
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