A ribonuclease specific for inosine‐containing RNA: a potential role in antiviral defence?

RNA transcripts in which all guanosine residues are replaced by inosine are degraded at a highly accelerated rate when incubated in extracts from HeLa cells, sheep uterus or pig brain. We report here the partial purification and characterization of a novel ribonuclease, referred to as I‐RNase, that is responsible for the degradation of inosine‐containing RNA (I‐RNA). I‐RNase is Mg 2+ dependent and specifically degrades single‐stranded I‐RNA. Comparison of the K m of the enzyme for I‐RNA with the K i for inhibition by normal RNA suggests a ∼300‐fold preferential binding to I‐RNA, which can account for the specificity of degradation. The site of cleavage by I‐RNase is non‐specific; I‐RNase acts as a 3′→5′ exonuclease generating 5′‐NMPs as products. The presence of alternative unconventional nucleotides in RNA does not result in degradation unless inosine residues are also present. We show that I‐RNase is able to degrade RNAs that previously have been modified by the RED‐1 double‐stranded RNA adenosine deaminase (dsRAD). dsRADs destabilize dsRNA by converting adenosine to inosine, and some of these enzymes are interferon inducible. We therefore speculate that I‐RNase in concert with dsRAD may form part of a novel cellular antiviral defence mechanism that acts to degrade dsRNA.