title: A ribonuclease specific for inosine-containing RNA: a potential role in antiviral defence?
abstract: 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 Mg2+ dependent and specifically degrades single-stranded I-RNA. Comparison of the Km of the enzyme for I-RNA with the Ki for inhibition by normal RNA suggests a approximately 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.
authors.affiliation: Department of Biochemistry, University of Cambridge, UK.
authors.forename: A D
authors.initials: AD
authors.lastname: Scadden
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D005095:Exoribonucleases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D007288:Inosine / Q000378:metabolism*; D007700:Kinetics; D008274:Magnesium; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000201:enzymology; D012330:RNA, Double-Stranded / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins; D012756:Sheep; D013379:Substrate Specificity; D013552:Swine; D014599:Uterus / Q000201:enzymology
chemical_list: D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D007288:Inosine; D005095:Exoribonucleases; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D008274:Magnesium