Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein‐Barr virus small RNA EBER‐1

Epstein–Barr virus (EBV) is a potent mitogenic and antiapoptotic agent for B lymphocytes and is associated with several different types of human tumour. The abundantly expressed small viral RNA, EBER‐1, binds to the growth inhibitory and pro‐apoptotic protein kinase R (PKR) and blocks activation of the latter by double‐stranded RNA. Recent evidence has suggested that expression of EBER‐1 alone in EBV‐negative B cells promotes a tumorigenic phenotype and that this may be related to inhibition of the pro‐apoptotic effects of PKR. The ribosomal protein L22 binds to EBER‐1 in virus‐infected cells, but the significance of this has not previously been established. We report here that L22 and PKR compete for a common binding site on EBER‐1. As a result of this competition, L22 interferes with the ability of the small RNA to inhibit the activation of PKR by dsRNA. Transient expression of EBER‐1 in murine embryonic fibroblasts stimulates reporter gene expression and partially reverses the inhibitory effect of PKR. However, EBER‐1 is also stimulatory when transfected into PKR knockout cells, suggesting an additional, PKR‐independent, mode of action of the small RNA. Expression of L22 prevents both the PKR‐dependent and ‐independent effects of EBER‐1 in vivo. These results suggest that the association of L22 with EBER‐1 in EBV‐infected cells can attenuate the biological effects of the viral RNA. Such effects include both the inhibition of PKR and additional mechanism(s) by which EBER‐1 stimulates gene expression.