Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily.
Angiogenin is a 14.4-kDa human plasma protein with 65% homology to RNase A that retains the key active site residues and three of the four RNase A disulfide bonds. We demonstrate that recombinant angiogenin functions as a cytotoxic tRNA-specific RNase in cell-free lysates and when injected into Xenopus oocytes. Inhibition of protein synthesis by angiogenin correlates with degradation of endogenous oocyte tRNA. Exogenous, radiolabeled tRNA is also hydrolyzed by angiogenin, whereas oocyte rRNA and mRNA are not detectably degraded by angiogenin. Protein synthesis was restored to angiogenin-injected oocytes by injecting the RNase inhibitor RNasin plus total Xenopus or calf liver tRNAs, thereby demonstrating that the tRNA degradation induced by angiogenin was the sole cause of cytotoxicity. A similar tRNA-reversible inhibition of protein synthesis was seen in rabbit reticulocyte lysates. Angiogenin therefore appears to be a specific cellular tRNase, whereas five homologues in the RNase A superfamily lack angiogenin's specificity for tRNA. One of these homologues purified from human eosinophils, eosinophil-derived neurotoxin, nonspecifically degrades oocyte RNA similar to RNase A and is also cytotoxic at very low concentrations.
Saxena
S K
SK
Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Rybak
S M
SM
Davey
R T
RT
Youle
R J
RJ
Ackerman
E J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002470:Cell Survival; D003603:Cytotoxins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011506:Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D003603:Cytotoxins; D011506:Proteins; D012343:RNA, Transfer; D012260:Ribonucleases; C046366:angiogenin; D012259:Ribonuclease, Pancreatic