Angiogenin-induced tRNA fragments inhibit translation initiation

By P. Ivanov, M. Emara, J. Villén, Steven P. Gygi, Paul Anderson. Molecules and Cells, 2011

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SUMMARY 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-eIF2α 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 m7G 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/189b43b445024c102d949597d10a60b5d1629663