TAR RNA-binding protein is an inhibitor of the interferon-induced protein kinase PKR

Heesung Park, Monique V. Davies, Jeffrey Langland, Hwai Wen Chang, Yong Suk Nam, James Tartaglia, Enzo Paoletti, Bertram Jacobs, Randal J. Kaufman, Sundararajan Venkatesan

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Abstract

A cDNA encoding a double-stranded-RNA (dsRNA)-binding protein was isolated by screening a HeLa cell cDNA expression library for proteins that bind the HIV-1 Rev-responsive-element RNA. The cDNA encoded a protein that was identical to TRBP, the previously reported cellular protein that binds the transactivation response element (TAR) RNA of human immunodeficiency virus type 1. TRBP inhibited phosphorylation of the interferon-induced ribosome- associated protein kinase PKR and of the eukaryotic translation initiation factor eIF-2α in a transient-expression system in which the translation of a reporter gene was inhibited by the localized activation of PKR. TRBP expression in HeLa cells complemented the growth and protein-synthesis defect of a vaccinia virus mutant lacking the expression of the dsRNA-binding protein E3L. These results 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.

Original languageEnglish (US)
Pages (from-to)4713-4717
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number11
DOIs
StatePublished - May 24 1994

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