TAR RNA-BINDING PROTEIN IS AN INHIBITOR OF THE INTERFERON-INDUCED PROTEIN-KINASE PKR

A cDNA encoding a double-stranded-RNA (dsRNA)-binding protein was isol ated by screening a HeLa cell cDNA expression library for proteins tha t bind the HIV-1 Rev-responsive-element RNA. The cDNA encoded a protei n that was identical to TRBP, the previously reported cellular protein that binds the transactivation response element (TAR) RNA of human im munodeficiency virus type 1. TRBP inhibited phosphorylation of the int erferon-induced ribosome-associated protein kinase ERR and of the euka ryotic translation initiation factor eIF-2 alpha in a transient-expres sion system in which the translation of a reporter gene was inhibited by the localized activation of ERR. TRBP expression in HeLa cells comp lemented the growth and protein-synthesis defect of a vaccinia virus m utant lacking the expression of the dsRNA-binding protein E3L. These r esults implicate TRBP as a cellular regulatory protein that binds RNAs containing specific secondary structure(s) to mediate the inhibition of PKR activation and stimulate translation in a localized manner.