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Mol Cell. 2011 Aug 19;43(4):613-23. doi: 10.1016/j.molcel.2011.06.022.

Angiogenin-induced tRNA fragments inhibit translation initiation.

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  • 1Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA. pivanov@rics.bwh.harvard.edu

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-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 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.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21855800
[PubMed - indexed for MEDLINE]
PMCID:
PMC3160621
Free PMC Article
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