Pancreatic-type ribonucleases (ptRNases) comprise a class of highly conserved secretory endoribonucleases in vertebrates. The prototype of this enzyme family is ribonuclease 1 (RNase 1). Understanding the physiological roles of RNase 1 is becoming increasingly important, as engineered forms of the enzyme progress through clinical trials as chemotherapeutic agents for cancer. Here, we present an in-depth biochemical characterization of RNase 1 homologs from a broad range of mammals (human, bat, squirrel, horse, cat, mouse, and cow) and nonmammalian species (chicken, lizard, and frog). We discover that the human homolog of RNase 1 has a pH optimum for catalysis, ability to degrade double-stranded RNA, and affinity for cell-surface glycans that are distinctly higher than those of its homologs. These attributes have relevance for human health. Moreover, the functional diversification of the 10 RNase 1 homologs illuminates the regulation of extracellular RNA and other aspects of vertebrate evolution.
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July 2017
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The model of amorpha-4,11-diene synthase at the background of Artemisia annua plant, and several key sesquiterpene products generated by our mutation to demonstrate how cyclization processes catalyzed by amorpha-4,11-diene synthase. For more information, please see article by Xiao-Ya Chen et al., pages 2191–2202.
Research Article|
June 21 2017
Comparative functional analysis of ribonuclease 1 homologs: molecular insights into evolving vertebrate physiology
Jo E. Lomax;
Jo E. Lomax
*
1Graduate Program in Cell and Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI, U.S.A.
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Chelcie H. Eller;
Chelcie H. Eller
*
2Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, U.S.A.
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Ronald T. Raines
2Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, U.S.A.
3Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI, U.S.A.
Correspondence: Ronald T. Raines (rtraines@wisc.edu)
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Publisher: Portland Press Ltd
Received:
March 03 2017
Revision Received:
April 30 2017
Accepted:
May 10 2017
Accepted Manuscript online:
May 11 2017
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem J (2017) 474 (13): 2219–2233.
Article history
Received:
March 03 2017
Revision Received:
April 30 2017
Accepted:
May 10 2017
Accepted Manuscript online:
May 11 2017
Citation
Jo E. Lomax, Chelcie H. Eller, Ronald T. Raines; Comparative functional analysis of ribonuclease 1 homologs: molecular insights into evolving vertebrate physiology. Biochem J 1 July 2017; 474 (13): 2219–2233. doi: https://doi.org/10.1042/BCJ20170173
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