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

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


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cats
  • Cattle
  • Chickens
  • Evolution, Molecular*
  • Horses
  • Humans
  • Mice
  • Phylogeny
  • RNA / metabolism*
  • Ranidae
  • Ribonucleases / metabolism*
  • Sequence Homology, Amino Acid
  • Vertebrates / physiology*


  • RNA
  • Ribonucleases