Deletions at the C-terminus of interferon γ reduce RNA binding and activation of double-stranded-RNA cleavage by bovine seminal ribonuclease

Abstract

Recombinant interferon γ (IFN-γ) from three species activates the cleavage of double stranded (ds-) RNA by the dimeric RNAase isolated from bovine semen (BS-RNAase). Human and bovine IFN-γ bind RNA tightly enough to inhibit cleavage by RNAase A. Murine IFN-γ and a proteolytic fragment of human IFN-γ, both of which lack part of the positively charged C-terminus, bind RNA weakly and do not inhibit RNAase A. Their ability to activate BS-RNAase is proportional to their activity in the anti-viral assay. Two monoclonal antibodies that neutralize the anti-viral activity of human IFN-γ inhibit the activation of BS-RNAase by both full-length and proteolysed human IFN-γ. Our results demonstrate that the C-terminus of IFN-γ contributes to RNA binding and activation of BS-RNAase, as well as to anti-viral activity.