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J Biol Chem. 2014 Sep 19;289(38):25996-6006. doi: 10.1074/jbc.M114.566166. Epub 2014 Jul 30.

Bovine brain ribonuclease is the functional homolog of human ribonuclease 1.

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From the Departments of Biochemistry and.
the Graduate Program in Cellular and Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706.
From the Departments of Biochemistry and Chemistry, and


Mounting evidence suggests that human pancreatic ribonuclease (RNase 1) plays important roles in vivo, ranging from regulating blood clotting and inflammation to directly counteracting tumorigenic cells. Understanding these putative roles has been pursued with continual comparisons of human RNase 1 to bovine RNase A, an enzyme that appears to function primarily in the ruminant gut. Our results imply a different physiology for human RNase 1. We demonstrate distinct functional differences between human RNase 1 and bovine RNase A. Moreover, we characterize another RNase 1 homolog, bovine brain ribonuclease, and find pronounced similarities between that enzyme and human RNase 1. We report that human RNase 1 and bovine brain ribonuclease share high catalytic activity against double-stranded RNA substrates, a rare quality among ribonucleases. Both human RNase 1 and bovine brain RNase are readily endocytosed by mammalian cells, aided by tight interactions with cell surface glycans. Finally, we show that both human RNase 1 and bovine brain RNase are secreted from endothelial cells in a regulated manner, implying a potential role in vascular homeostasis. Our results suggest that brain ribonuclease, not RNase A, is the true bovine homolog of human RNase 1, and provide fundamental insight into the ancestral roles and functional adaptations of RNase 1 in mammals.


Double-stranded RNA (dsRNA); Enzyme Catalysis; Heparin-binding Protein; RNA; Ribonuclease

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