Angiogenin-induced tRNA fragments inhibit translation initiation.
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Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P
Angiogenin-induced tRNA fragments inhibit translation initiation.
Mol Cell. 2011 Aug 19;43(4):613-23. doi: 10.1016/j.molcel.2011.06.022.
- PubMed ID
- 21855800 [ View in PubMed]
- Abstract
Angiogenin is a stress-activated ribonuclease that cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs). Transfection of natural or synthetic tiRNAs inhibits protein synthesis and triggers the phospho-eIF2alpha-independent assembly of stress granules (SGs), essential components of the stress response program. We show that selected tiRNAs inhibit protein synthesis by displacing eIF4G/eIF4A from uncapped > capped RNAs. tiRNAs also displace eIF4F, but not eIF4E:4EBP1, from isolated m(7)G cap. We identify a terminal oligoguanine motif that is required to displace the eIF4F complex, inhibit translation, and induce SG assembly. We show that the tiRNA-associated translational silencer YB-1 contributes to angiogenin-, tiRNA-, and oxidative stress-induced translational repression. Our data reveal some of the mechanisms by which stress-induced tRNA cleavage inhibits protein synthesis and activates a cytoprotective stress response program.