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PMID: 7901835 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Comparative analysis of the regulation of the interferon-inducible protein kinase PKR by Epstein-Barr virus RNAs EBER-1 and EBER-2 and adenovirus VAI RNA.

Nucleic acids research ·Vol. 21 ·No. 19 ·1993-09-25 ·Pages 4483-90

Sharp TV, Schwemmle M, Jeffrey I, Laing K, Mellor H, Proud CG, Hilse K, Clemens MJ

Abstract

The interferon-inducible protein kinase PKR interacts with a number of small viral RNA species, including adenovirus VAI RNA and the Epstein-Barr virus-encoded RNA EBER-1. These RNAs bind to PKR and protect protein synthesis from inhibition by double-stranded RNA in the reticulocyte lysate system. Using a peptide phosphorylation assay we show here that EBER-1, like VAI, directly inhibits the activation of purified PKR. A second Epstein-Barr virus RNA, EBER-2, also regulates PKR. EBER-1, EBER-2 and VAI RNA exhibit mutually competitive binding to the native or recombinant enzyme, as assessed by U.V. crosslinking experiments and filter binding assays. The affinities of all three RNAs for PKR in vitro are similar (Kd = ca. 0.3 nM). Since this protein kinase has been proposed to exert a tumour suppressor function in vivo, the ability of EBER-1 to inhibit its activation suggests a role for this small RNA in cell transformation by Epstein-Barr virus.

MeSH Terms
Adenoviridae/genetics Amino Acid Sequence Animals Enzyme Activation/drug effects Herpesvirus 4, Human/genetics In Vitro Techniques Molecular Sequence Data Peptides/chemistry,metabolism Poly I-C/pharmacology Protein Biosynthesis Protein Serine-Threonine Kinases/antagonists & inhibitors,metabolism RNA, Viral/pharmacology RNA-Binding Proteins/metabolism Rabbits Recombinant Proteins/metabolism eIF-2 Kinase
Chemicals
Peptides RNA, Viral RNA-Binding Proteins Recombinant Proteins adenovirus associated RNA Protein Serine-Threonine Kinases eIF-2 Kinase Poly I-C
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Sharp T V
Department of Cellular and Molecular Sciences, St George's Hospital Medical School, London, UK.
Schwemmle M
Jeffrey I
Laing K
Mellor H
Proud C G
Hilse K
Clemens M J
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/21.19.4483
Published
1993-09-25
Pages
4483-90
Language
English
Region
England
NLM ID
0411011
PMCID
PMC311179
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1093/nar/21.19.4483 PMC Full Text View journal details
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