Activation of RNA Polymerase III Transcription in Cells Transformed by Simian Virus 40

Abstract

RNA polymerase (Pol) III transcription is abnormally active in fibroblasts that have been transformed by simian virus 40 (SV40). This report presents evidence that two separate components of the general Pol III transcription apparatus, TFIIIB and TFIIIC2, are deregulated following SV40 transformation. TFIIIC2 subunits are expressed at abnormally high levels in SV40-transformed cells, an effect which is observed at both protein and mRNA levels. In untransformed fibroblasts, TFIIIB is subject to repression through association with the retinoblastoma protein RB. The interaction between RB and TFIIIB is compromised following SV40 transformation. Furthermore, the large T antigen of SV40 is shown to relieve repression by RB. The E7 oncoprotein of human papillomavirus can also activate Pol III transcription, an effect that is dependent on its ability to bind to RB. The data provide evidence that both TFIIIB and TFIIIC2 are targets for activation by DNA tumor viruses.

ACKNOWLEDGMENTS

We are extremely grateful to K. Vousden and R. Watson for the E7 expression vectors, D. Lane for recombinant T antigen, N. Hernandez for antibody SL30, and Y. Shen and A. Berk for antibodies Ab2 and Ab4.

This work was funded by grant SP2314/0101 to R.J.W. from the Cancer Research Campaign and grant 98-46 to R.J.W. from the Association for International Cancer Research. J.E.S. and Z.A.F-E. are supported by postgraduate studentships from the Biotechnology and Biological Sciences Research Council and the Medical Research Council, respectively. R.J.W. is a Jenner Research Fellow of the Lister Institute of Preventive Medicine.