Cell Biology

Signals of Stress

See allHide authors and affiliations

Science  01 May 2009:
Vol. 324, Issue 5927, pp. 568
DOI: 10.1126/science.324_568c

Two papers have identified a signaling function for ribonucleases in stress. During times of stress, protein synthesis is inhibited via phosphorylation of eukaryotic translation initiation factor 2A (eIF2A). Yamasaki et al. focused on observations that translational arrest can occur in cells that express a mutant eIF2A that lacks the phosphorylation site. They found that cells exposed to oxidative stress accumulated cleavage products of transfer RNA (tRNA). Angiogenin is a secreted ribonuclease that has been implicated in tumorigenesis because it promotes the formation of blood vessels, and the authors found that depleting cells of angiogenin inhibited the stress-induced cleavage of tRNA. Thus, stressed cells may signal their neighbors by secreting angiogenin.

Yeast cells also cleave tRNA when exposed to oxidative stress, and Thompson and Parker have identified Rny1 as the ribonuclease responsible. Rny1 was released from the vacuole into the cytoplasm in response to oxidative stress, and overexpression of Rny1 caused apoptosis (cell death) in yeast. Nevertheless, Rny1 must do more than cleave tRNAs, because mutants that lacked catalytic activity could still promote cell death. Intriguingly, the human ortholog of Rny1, RNASET2, has a tumor-suppressing activity that is independent of its catalytic activity. Thus, it appears that release of Rny1 from the vacuole (analogous to the apoptotic release of cytochrome c from mitochondria) both causes cleavage of cytoplasmic tRNAs and affects signaling pathways controlling cell death.

J. Cell Biol. 185, 35; 43 (2009).

Navigate This Article