Cell
Volume 72, Issue 5, 12 March 1993, Pages 753-765
Journal home page for Cell

Article
Expression cloning of 2-5A-dependent RNAase: A uniquely regulated mediator of interferon action

https://doi.org/10.1016/0092-8674(93)90403-DGet rights and content

Abstract

2-5A-dependent RNAase, an interferon-induced enzyme that is activated by 5′-phosphorylated, 2′,5′-linked oligoadenylates (2-5A), is implicated in both the molecular mechanisms of interferon action and the fundamental control of RNA stability in mammalian cells. Here we report the expression cloning and analysis of murine and human 2-5A-dependent RNAases. The 2-5A binding properties and RNAase activities of recombinant and naturally occurring forms of 2-5A-dependent RNAase were identical. Interferon induction of 2-5A-dependent RNAase expression was demonstrated by measuring the mRNA levels in cells treated with interferon and cycloheximide. Analysis of aligned murine and human 2-5A-dependent RNAase sequences revealed several intriguing features, including similarity to RNAase E, which is implicated in the control of mRNA stability in E. coli. Interestingly, a duplicated phosphate-binding loop motif was determined by deletion analysis and site-directed mutagenesis to function in the binding of 2-5A.

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