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

Research output: Contribution to journalArticle

164 Citations (Scopus)

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

Fingerprint

eIF-2 Kinase
RNA-Binding Proteins
Response Elements
Interferons
Transcriptional Activation
RNA
Proteins
HeLa Cells
HIV-1
Prokaryotic Initiation Factor-2
Complementary DNA
Eukaryotic Initiation Factors
env Genes
Vaccinia virus
Gene Library
Ribosomes
Reporter Genes
Phosphorylation
Growth

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

TAR RNA-binding protein is an inhibitor of the interferon-induced protein kinase PKR. / Park, Heesung; Davies, Monique V.; Langland, Jeffrey; Chang, Hwai Wen; Nam, Yong Suk; Tartaglia, James; Paoletti, Enzo; Jacobs, Bertram; Kaufman, Randal J.; Venkatesan, Sundararajan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 11, 24.05.1994, p. 4713-4717.

Research output: Contribution to journalArticle

Park, Heesung ; Davies, Monique V. ; Langland, Jeffrey ; Chang, Hwai Wen ; Nam, Yong Suk ; Tartaglia, James ; Paoletti, Enzo ; Jacobs, Bertram ; Kaufman, Randal J. ; Venkatesan, Sundararajan. / TAR RNA-binding protein is an inhibitor of the interferon-induced protein kinase PKR. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 11. pp. 4713-4717.
@article{c076277969e94d59b1a25eb5689dbea2,
title = "TAR RNA-binding protein is an inhibitor of the interferon-induced protein kinase PKR",
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.",
author = "Heesung Park and Davies, {Monique V.} and Jeffrey Langland and Chang, {Hwai Wen} and Nam, {Yong Suk} and James Tartaglia and Enzo Paoletti and Bertram Jacobs and Kaufman, {Randal J.} and Sundararajan Venkatesan",
year = "1994",
month = "5",
day = "24",
doi = "10.1073/pnas.91.11.4713",
language = "English (US)",
volume = "91",
pages = "4713--4717",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "11",

}

TY - JOUR

T1 - TAR RNA-binding protein is an inhibitor of the interferon-induced protein kinase PKR

AU - Park, Heesung

AU - Davies, Monique V.

AU - Langland, Jeffrey

AU - Chang, Hwai Wen

AU - Nam, Yong Suk

AU - Tartaglia, James

AU - Paoletti, Enzo

AU - Jacobs, Bertram

AU - Kaufman, Randal J.

AU - Venkatesan, Sundararajan

PY - 1994/5/24

Y1 - 1994/5/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028242864&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028242864&partnerID=8YFLogxK

U2 - 10.1073/pnas.91.11.4713

DO - 10.1073/pnas.91.11.4713

M3 - Article

VL - 91

SP - 4713

EP - 4717

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 11

ER -