Angiogenin-Induced tRNA Fragments Inhibit Translation Initiation

Pavel Ivanov, Mohamed Emara, Judit Villen, Steven P. Gygi, Paul Anderson

Research output: Contribution to journalArticle

332 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)613-623
Number of pages11
JournalMolecular Cell
Volume43
Issue number4
DOIs
Publication statusPublished - 19 Aug 2011
Externally publishedYes

Fingerprint

Transfer RNA
Anticodon
Proteins
Ribonucleases
Transfection
Oxidative Stress
RNA
angiogenin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Angiogenin-Induced tRNA Fragments Inhibit Translation Initiation. / Ivanov, Pavel; Emara, Mohamed; Villen, Judit; Gygi, Steven P.; Anderson, Paul.

In: Molecular Cell, Vol. 43, No. 4, 19.08.2011, p. 613-623.

Research output: Contribution to journalArticle

Ivanov, Pavel ; Emara, Mohamed ; Villen, Judit ; Gygi, Steven P. ; Anderson, Paul. / Angiogenin-Induced tRNA Fragments Inhibit Translation Initiation. In: Molecular Cell. 2011 ; Vol. 43, No. 4. pp. 613-623.
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