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

T V Sharp, M Schwemmle, I Jeffrey, K Laing, H Mellor, C G Proud, K Hilse, M J Clemens

Research output: Contribution to journalArticle (Academic Journal)

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.

Original languageEnglish
Pages (from-to)4483-90
Number of pages8
JournalNucleic Acids Research
Volume21
Issue number19
DOIs
Publication statusPublished - 25 Sep 1993

Keywords

  • Adenoviridae/genetics
  • Amino Acid Sequence
  • Animals
  • Enzyme Activation/drug effects
  • Herpesvirus 4, Human/genetics
  • In Vitro Techniques
  • Molecular Sequence Data
  • Peptides/chemistry
  • Poly I-C/pharmacology
  • Protein Biosynthesis
  • Protein-Serine-Threonine Kinases/antagonists & inhibitors
  • RNA, Viral/pharmacology
  • RNA-Binding Proteins/metabolism
  • Rabbits
  • Recombinant Proteins/metabolism
  • eIF-2 Kinase

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