Silencing an inhibitor unleashes a cytotoxic enzyme.

ABSTRACT

The ribonuclease inhibitor (RI) is a cytosolic protein and a potent inhibitor of bovine pancreatic ribonuclease (RNase A). Amphibian homologues and variants of RNase A that evade RI are cytotoxic. Here, we employ RNA interference along with amphibian and mammalian ribonucleases to demonstrate that RI protects cells against exogenous ribonucleases. These data indicate an imperative for the molecular evolution of RI and suggest a means of enhancing the cytotoxicity of mammalian ribonucleases.