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J. Biol. Chem., Vol. 281, Issue 45, 33871-33880, November 10, 2006

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Epstein-Barr Virus Induces Cellular Transcription Factors to Allow Active Expression of EBER Genes by RNA Polymerase III^*

Zoë A. Felton-Edkins, Alexander Kondrashov, Dimitra Karali, Jennifer A. Fairley, Christopher W. Dawson, John R. Arrand, Lawrence S. Young, and Robert J. White^¶1

From the Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow G12 8QQ, Cancer Research UK Institute for Cancer Studies, University of Birmingham Medical School, Birmingham, B15 2TT, and ^¶Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, United Kingdom

The EBER genes of Epstein-Barr virus (EBV) are transcribed by RNA polymerase (pol) III to produce untranslated RNAs that are implicated in oncogenesis. These EBER transcripts are the most highly expressed viral gene products in EBV-transformed cells. We have identified changes to the cellular transcription machinery that may contribute to the high levels of EBER RNA. These include phosphorylation of ATF2, which interacts with EBER promoters. A second is induction of TFIIIC, a pol III-specific factor that activates EBER genes; all five subunits of TFIIIC are overexpressed in EBV-positive cells. In addition, EBV induces BDP1, a subunit of the pol III-specific factor TFIIIB. Although BDP1 is the only TFIIIB subunit induced by EBV, its induction is sufficient to stimulate EBER expression in vivo, implying a limiting function. The elevated levels of BDP1 and TFIIIC in EBV-positive cells stimulate production of tRNA, 7SL, and 5S rRNA. Abnormally high expression of these cellular pol III products may contribute to the ability of EBV to enhance growth potential.

Received for publication, January 17, 2006 , and in revised form, August 30, 2006.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 44-141-330-3953; Fax: 44-141-942-6521; E-mail: rwhite{at}udcf.gla.ac.uk.

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