HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print January 22, 2008

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.1107725v1 83/5/1079    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rosenberg, H. F. Search for Related Content PubMed PubMed Citation Articles by Rosenberg, H. F.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1107725

Received for publication November 2, 2007.
Revised November 28, 2007.
Accepted for publication November 29, 2007.

Article

RNase A ribonucleases and host defense: an evolving story

Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

^@ To whom correspondence should be addressed. E-mail: hrosenberg{at}niaid.nih.gov.

	Abstract

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 RNases 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 RNases, recent experimental findings, and important questions for the near and distant future will be reviewed.

Key Words: leukocyte • cationic • eosinophil • evolution • bactericidal • virus