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Human Angiogenin Is a Potent Cytotoxin in the Absence of Ribonuclease Inhibitor

Sydney P Thomas, Trish T Hoang, Valerie T Ressler, Ronald T Raines

RNA. 2018 Aug;24(8):1018-1027.

PMID: 29748193

Abstract:

Angiogenin (ANG) is a secretory ribonuclease that promotes the proliferation of endothelial cells, leading to angiogenesis. This function relies on its ribonucleolytic activity, which is low for simple RNA substrates. Upon entry into the cytosol, ANG is sequestered by the ribonuclease inhibitor protein (RNH1). We find that ANG is a potent cytotoxin for RNH1-knockout HeLa cells, belying its inefficiency as a nonspecific catalyst. The toxicity does, however, rely on the ribonucleolytic activity of ANG and a cytosolic localization, which lead to the accumulation of particular tRNA fragments (tRFs), such as tRF-5 Gly-GCC. These up-regulated tRFs are highly cytotoxic at physiological concentrations. Although ANG is well-known for its promotion of cell growth, our results reveal that ANG can also cause cell death.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4248743 Angiogenin human Angiogenin human Price
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