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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Angiogenin-Induced tRNA Fragments Inhibit Translation Initiation
Molecular Cell, Volume 43, No. 4, Year 2011
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Description
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 7G 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. © 2011 Elsevier Inc.
Authors & Co-Authors
Ivanov, Pavel V.
United States, Boston
Brigham and Women's Hospital
United States, Boston
Harvard Medical School
Emara, Mohamed M.
United States, Boston
Brigham and Women's Hospital
United States, Boston
Harvard Medical School
Egypt, Giza
Faculty of Veterinary Medicine
Villén, Judit
United States, Boston
Harvard Medical School
United States, Seattle
University of Washington
Gygi, Steven P.
United States, Boston
Harvard Medical School
Anderson, Paul J.
United States, Boston
Brigham and Women's Hospital
United States, Boston
Harvard Medical School
Statistics
Citations: 791
Authors: 5
Affiliations: 4
Identifiers
Doi:
10.1016/j.molcel.2011.06.022
ISSN:
10972765
e-ISSN:
10974164