RNase A ribonucleases and host defense: an evolving story.
RNase A (bovine pancreatic RNase) is the founding member an extensive family of divergent proteins that share specific elements of sequence homology, a unique disulfide-bonded tertiary structure, and the ability to hydrolyze polymeric RNA. Among the more intriguing and perhaps counterintuitive findings, at the current state of the art, the connection between RNase activity and characterized host defense functions is quite weak; whether this is a scientific reality or more a reflection of what has been chosen for study remains to be determined. Several of the RNase A family RNases are highly cationic and have cytotoxic and bactericidal properties that are clearly (eosinophil cationic protein, leukocyte RNase A-2) or are probably (RNase 7) unrelated to their enzymatic activity. Interestingly, peptides derived from the leukocyte RNase A-2 sequence are nearly as bactericidal as the entire protein, suggesting that among other functions, the RNase A superfamily may be serving as a source of gene scaffolds for the generation of novel cytotoxic peptides. Other RNase A ribonucleases are somewhat less cationic (mouse angiogenin 4, zebrafish RNases) and have moderate bactericidal activities that have not yet been explored mechanistically. Additional host defense functions characterized specifically for the RNase eosinophil-derived neurotoxin include reducing infectivity of RNA viruses for target cells in culture, which does require RNase activity, chemoattraction of immature human dendritic cells via a G-protein-coupled receptor-dependent mechanism, and activation of TLR2. The properties of individual RNase A ribonucleases, recent experimental findings, and important questions for the near and distant future will be reviewed.
Rosenberg
Helene F
HF
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. hrosenberg@niaid.nih.gov
D000818:Animals; D002417:Cattle; D002645:Chickens; D047150:Eosinophil Cationic Protein / Q000378:metabolism; D004804:Eosinophils / Q000201:enzymology; D007962:Leukocytes / Q000201:enzymology; D008322:Mammals; D010179:Pancreas / Q000201:enzymology; D011892:Rana catesbeiana; D012259:Ribonuclease, Pancreatic / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism; D015027:Zebrafish
D012260:Ribonucleases; D047150:Eosinophil Cationic Protein; C470000:Ribonuclease 7; C046366:angiogenin; D012259:Ribonuclease, Pancreatic