Analysis and origins of the human and mouse RNase L genes: mediators of interferon action

The 2',5'-oligoadenylate-activated enzyme, RNase L, is an endoribonuclease implicated in the antiviral and apoptotic activities of interferons. To pro be the genetics of the 2-5A system, the human and mouse genes were cloned, characterized, and compared. The first coding exon of both genes encodes th e regulatory regions of RNase L, 67-70% of the proteins including nine anky rin repeats, the 2-5A binding domain, and several protein kinase homology m otifs. In contrast, the coding sequence for the ribonuclease domain in the mouse and human gene is divided among three exons. The transcriptional star t site of the human RNase L gene was located in noncoding exon I by primer extension analysis. A complete coding sequence of mouse RNase L was obtaine d revealing a 735-amino acid protein with 64% identity to human RNase L. A hypothesis is presented concerning the evolutionary relationship of RNase L to both an ankyrin repeat protein kinase and the kinase-endoribonuclease, IRE1, that mediates the unfolded protein response.