ADENOVIRUS VAI RNA ANTAGONIZES THE RNA-EDITING ACTIVITY OF THE ADAR ADENOSINE-DEAMINASE

The virus-associated VAI RNA of adenovirus is a small highly structure d RNA that is required for the efficient translation of cellular and v iral mRNAs at late times after infection. VAI RNA antagonizes the acti vation of the interferon-inducible RNA-dependent protein kinase, PKR, an important regulator of translation. The RNA-specific adenosine deam inase, ADAR, is an interferon-inducible RNA-editing enzyme that cataly zes the site-selective C-6 deamination of adenosine to inosine. ADAR p ossesses three copies of the highly conserved RNA-binding motif (dsRBM ) that are similar to the two copies found in PKR, the enzyme in which the prototype dsRBM motif was discovered. We have examined the effect of VAI RNA on ADAR function. VAI RNA impairs the activity of ADAR dea minase. This inhibition can be observed in extracts prepared from inte rferon-treated human cells and from monkey COS cells in which wild-typ e recombinant ADAR was expressed. Analysis of wild-type and mutant for ms of VA RNA suggests that the central domain is important in the anta gonism of ADAR activity. These results suggest that VAI RNA may modula te viral and cellular gene expression by modulating RNA editing as wel l as mRNA translation. (C) 1998 Academic Press.