Angiogenin cleaves tRNA and promotes stress-induced translational repression

By S. Yamasaki, P. Ivanov, G. Hu, Paul Anderson. Journal of Cell Biology, 2009

907 citations recorded by the source corpus.

Stress-induced phosphorylation of eIF2α inhibits global protein synthesis to conserve energy for repair of stress-induced damage. Stress-induced translational arrest is observed in cells expressing a nonphosphorylatable eIF2α mutant (S51A), which indicates the existence of an alternative pathway of translational control. In this paper, we show that arsenite, heat shock, or ultraviolet irradiation promotes transfer RNA (tRNA) cleavage and accumulation of tRNA-derived, stress-induced small RNAs (tiRNAs). We show that angiogenin, a secreted ribonuclease, is required for stress-induced production of tiRNAs. Knockdown of angiogenin, but not related ribonucleases, inhibits arsenite-induced tiRNA production and translational arrest. In contrast, knockdown of the angiogenin inhibitor RNH1 enhances tiRNA production and promotes arsenite-induced translational arrest. Moreover, recombinant angiogenin, but not RNase 4 or RNase A, induces tiRNA production and inhibits protein synthesis in the absence of exogenous stress. Finally, transfection of angiogenin-induced tiRNAs promotes phospho-eIF2α–independent translational arrest. Our results introduce angiogenin and tiRNAs as components of a phospho-eIF2α–independent stress response program.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/72dfb20bab03f1dab04917766dc9d6aa2543a837

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. J. Villén
2. Steven P. Gygi
3. P. Ivanov
4. Y. Shibata
5. Ankit Malhotra
6. Anindya Dutta
7. Yong Sun Lee
8. Paul Anderson

Citations in the corpus

• RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. (2010, background): “It has been established recently that ribonucleases play an important role in the stress-induced cleavage of tRNAs (Yamasaki et al. 2009), a mechanism that promotes the assembly of stress granules (Emara et al. 2010).”
• tRNA biology charges to the front. (2010, background): “First, Anderson and coworkers (Yamasaki et al. 2009) have shown that each of several different stress treatments of mammalian cells activates the ribonuclease angiogenin to cleave tRNA to produce tRNA-derived stress-induced RNAs (tiRNAs) that inhibit translation.”
• Angiogenin-induced tRNA fragments inhibit translation initiation (2011, methodology): “…Giardia lamblia (Li et al., 2008), spore-forming Aspergillus fumigatus (Jochl et al., 2008), phosphate-depleted Arabidopsis thaliana (Hsieh et al., 2010), and oxidatively stressed Saccharomyces cerevisiae (Thompson et al., 2008) and Homo sapiens (Thompson et al., 2008; Yamasaki et al., 2009).”
• A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). (2009, background): “These tRNA fragments are different from the ones reported here in that they are derived from a cleavage at or around the anti-codon loop by Rny1p in yeast (Thompson and Parker 2009) or angiogenin in humans (Yamasaki et al. 2009).”