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 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-2 alpha 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.
Park
H
H
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Davies
M V
MV
Langland
J O
JO
Chang
H W
HW
Nam
Y S
YS
Tartaglia
J
J
Paoletti
E
E
Jacobs
B L
BL
Kaufman
R J
RJ
Venkatesan
S
S
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D002628:Chemoreceptor Cells; D004790:Enzyme Induction; D029968:Escherichia coli Proteins; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface; D014616:Vaccinia virus / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000235:genetics; D019892:eIF-2 Kinase
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D015852:Eukaryotic Initiation Factor-2; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; C057331:Tar protein, E coli; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase