A stress-induced tyrosine-tRNA depletion response mediates codon-based translational repression and growth suppression.
EMBO J
; 40(2): e106696, 2021 01 15.
Article
in En
| MEDLINE
| ID: mdl-33346941
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tyrosine
/
Protein Biosynthesis
/
Codon
/
RNA, Transfer
Limits:
Animals
/
Humans
Language:
En
Journal:
EMBO J
Year:
2021
Document type:
Article
Affiliation country:
United States