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Biochem J. 2017 Jun 21;474(13):2219-2233. doi: 10.1042/BCJ20170173.

Comparative functional analysis of ribonuclease 1 homologs: molecular insights into evolving vertebrate physiology.

Author information

1
Graduate Program in Cell and Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI, U.S.A.
2
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, U.S.A.
3
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI, U.S.A. rtraines@wisc.edu.
4
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI, U.S.A.

Abstract

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.

KEYWORDS:

RNA; enzyme activity; enzymology; molecular evolution; protein structure; ribonuclease

PMID:
28495858
PMCID:
PMC5660862
DOI:
10.1042/BCJ20170173
[Indexed for MEDLINE]
Free PMC Article

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