Human angiogenin is a potent cytotoxin in the absence of ribonuclease inhibitor
Name
RNA-2018-Thomas-1018-27.pdf
Description
Published version
Size
3.43 MB
Format
Adobe PDF
Checksum (MD5)
1c8cc80bf64de9b1954386ddd5b1983d
Author(s)
Thomas, Sydney P
Hoang, Trish T
Ressler, Valerie T
Raines, Ronald T
Date Issued
2018
Journal
RNA
Publisher
Cold Spring Harbor Laboratory
Version
Final published version
Abstract
© 2018 Steiman-Shimony et al. 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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1261/RNA.065516.117
