COMPARATIVE-ANALYSIS OF THE REGULATION OF THE INTERFERON-INDUCIBLE PROTEIN-KINASE PKR BY EPSTEIN-BARR-VIRUS RNAS EBER-1 AND EBER-2 AND ADENOVIRUS VA(I) RNA

The interferon-inducible protein kinase PKR interacts with a number of small viral RNA species, including adenovirus VA, RNA and the Epstein - Barr virus-encoded RNA EBER-1. These RNAs bind to PKR and protect p rotein synthesis from inhibition by double-stranded RNA in the reticul ocyte lysate system. Using a peptide phosphorylation assay we show her e that EBER-1, like VA(I), directly inhibits the activation of purifie d PKR. A second Epstein - Barr virus RNA, EBER-2, also regulates PKR. EBER-1, EBER-2 and VA(I) RNA exhibit mutually competitive binding to t he native or recombinant enzyme, as assessed by U.V. crosslinking expe riments and filter binding assays. The affinities of all three RNAs fo r PKR in vitro are similar (K(d) = ca. 0.3 nM). Since this protein kin ase has been proposed to exert a tumour suppressor function in vivo, t he ability of EBER-1 to inhibit its activation suggests a role for thi s small RNA in cell transformation by Epstein - Barr virus.