Angiogenin-Induced tRNA Fragments Inhibit Translation Initiation

作者：Ivanov Pavel^*; Emara Mohamed M; Villen Judit; Gygi Steven P; Anderson Paul

来源：Molecular Cell, 2011, 43(4): 613-623.

DOI：10.1016/j.molcel.2011.06.022

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-elF2 alpha-independent assembly of stress granules (SGs), essential components of the stress response program. We show that selected tiRNAs inhibit protein synthesis by displacing elF4G/elF4A from uncapped > capped RNAs. tiRNAs also displace elF4F, but not elF4E:4EBP1, from isolated m(7)G cap. We identify a terminal oligoguanine motif that is required to displace the elF4F 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.

• 出版日期2011-8-19