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PMID: 21855800 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Angiogenin-induced tRNA fragments inhibit translation initiation.

Molecular cell ·Vol. 43 ·No. 4 ·2011-08-19 ·Pages 613-23

Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P

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.

MeSH Terms
Cell Line Eukaryotic Initiation Factor-4G/metabolism,physiology Humans Peptide Chain Initiation, Translational RNA, Transfer/chemistry,physiology Ribonuclease, Pancreatic/physiology Stress, Physiological Y-Box-Binding Protein 1/metabolism,physiology
Chemicals
EIF4G1 protein, human Eukaryotic Initiation Factor-4G Y-Box-Binding Protein 1 YBX1 protein, human RNA, Transfer angiogenin Ribonuclease, Pancreatic
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ivanov Pavel
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA. pivanov@rics.bwh.harvard.edu
Emara Mohamed M
Villen Judit
Gygi Steven P
Anderson Paul
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2011.06.022
Email
pivanov@rics.bwh.harvard.edu
Published
2011-08-19
Pages
613-23
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3160621
Subset
IM
Grants
NIAID NIH HHS · R56 AI033600 · United States
NIAID NIH HHS · R01 AI033600-11A2 · United States
NIAID NIH HHS · AI065858 · United States
NIAID NIH HHS · R01 AI033600 · United States
NIAID NIH HHS · AI033600 · United States
NIAID NIH HHS · P01 AI065858 · United States
NIAID NIH HHS · P01 AI065858-01A1 · United States
Corrections
CommentIn
PMID: 21855789
External Links
PubMed source DOI: 10.1016/j.molcel.2011.06.022 PMC Full Text View journal details
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