Introduction of 8-methyladenosine into 2', 5'-oligoadenylate (2-5A) 2'-terminus induces dramatic shift in binding site of RNase L

Abstract

The 2',5'-oligoadenylate (2-5A) system is an interferon (IFN)-regulated RNA decay pathway that provides innate immunity against viral infections. The biological action of the 2-5A system is mediated by RNase L, an endoribonuclease that becomes enzymatically active after binding to 2-5A. It has been reported that the 5'-phosphoryl group of 2-5A is required for RNase L activation. However, we have found that 5'-O-dephosphorylated 2-5A tetramer analogs with 8-methyladenosine at the 2'-terminus were more effective as an activator of RNase L than the parent 2-5A (p5'A2'p5'A2'p5'A2'p5'A2'). Introduction of 8-methyladenosine is thought to induce a dramatic shift in the binding site of RNase L.