Epstein-Barr virus induces cellular transcription factors to allow active expression of EBER genes by RNA polymerase III.
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.
Felton-Edkins
Zoë A
ZA
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Kondrashov
Alexander
A
Karali
Dimitra
D
Fairley
Jennifer A
JA
Dawson
Christopher W
CW
Arrand
John R
JR
Young
Lawrence S
LS
White
Robert J
RJ
D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D011401:Promoter Regions, Genetic / Q000235:genetics; D012320:RNA Polymerase III / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics*; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035361:Transcription Factor TFIIIB / Q000235:genetics / Q000378:metabolism; D019474:Transcription Factors, TFIII / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D000098832:Transcription Factor TFIIIC
C427472:BDP1 protein, human; D004268:DNA-Binding Proteins; C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D035361:Transcription Factor TFIIIB; D019474:Transcription Factors, TFIII; D000098832:Transcription Factor TFIIIC; D012320:RNA Polymerase III