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 probe 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 the regulatory regions of RNase L, 67-70% of the proteins including nine ankyrin repeats, the 2-5A binding domain, and several protein kinase homology motifs. In contrast, the coding sequence for the ribonuclease domain in the mouse and human gene is divided among three exons. The transcriptional start 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 obtained 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.