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

The Biochemical Journal
Jo E LomaxRonald T Raines

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.

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Citations

May 6, 2019·RNA·Emily R GarnettRonald T Raines
Jul 2, 2020·Nucleic Acids Research·Gal NechooshtanThomas R Gingeras
Jun 6, 2018·Frontiers in Immunology·Lu LuEster Boix
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Katrin Bedenbender, Bernd T Schmeck
Dec 19, 2019·Frontiers in Immunology·Giovanni Gotte, Marta Menegazzi
Oct 5, 2018·Molecular Cancer Therapeutics·Trish T HoangRonald T Raines
Jul 5, 2019·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Javier Oroz, Douglas V Laurents
Jan 5, 2021·Frontiers in Cell and Developmental Biology·Klaus T PreissnerElisabeth Deindl
Jan 18, 2021·International Journal of Biological Macromolecules·Jing ChenHan Liu
Oct 16, 2020·ACS Infectious Diseases·Chelcie H Eller, Ronald T Raines
Jan 12, 2019·Biochemistry·Valerie T Ressler, Ronald T Raines
Dec 10, 2020·Bioconjugate Chemistry·Jessica SayersRonald T Raines

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