Nucleic Acids Research, Vol 24, Issue 22 4471-4478, Copyright © 1996 by Oxford University Press
A Elia, KG Laing, A Schofield, VJ Tilleray and MJ Clemens
During the initial infection of B lymphocytes by Epstein-Barr virus (EBV)
only a few viral genes are expressed, six of which encode the EBV nuclear
antigens, EBNAs 1-6. The majority of EBNA mRNAs share common 5'- ends
containing a variable number of two alternating and repeated exons
transcribed from the BamHI W major internal repeats of the viral DNA. These
sequences can also exist as independent small RNA species in some
EBV-infected cell types. We present evidence that transcripts from these W
repeat regions can exert a trans-acting effect on protein synthesis,
through their ability to activate the dsRNA-dependent protein kinase PKR.
UV cross-linking and filter binding assays have demonstrated that the W
transcripts bind specifically to PKR and can compete with another
EBV-encoded small RNA, EBER-1, which was shown previously to bind this
kinase. In the reticulocyte lysate system the W RNAs shut off protein
synthesis through an ability to activate PKR. In contrast to EBER-1, the W
RNAs are unable to block the dsRNA-dependent activation of PKR. Using a
purified preparation of the protein kinase we have shown that the W
transcripts directly activate PKR in vitro. The results suggest that EBV
has the ability both to activate and to inhibit PKR through the actions of
different products of viral transcription.
ARTICLES
Regulation of the double-stranded RNA-dependent protein kinase PKR by RNAs encoded by a repeated sequence in the Epstein-Barr virus genome
Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, London, UK.
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