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PMID: 11094071 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Retinoblastoma protein disrupts interactions required for RNA polymerase III transcription.

Molecular and cellular biology ·Vol. 20 ·No. 24 ·2000-12-00 ·Pages 9192-202

Sutcliffe JE, Brown TR, Allison SJ, Scott PH, White RJ

Abstract

The retinoblastoma protein (RB) has been shown to suppress RNA polymerase (Pol) III transcription in vivo (R. J. White, D. Trouche, K. Martin, S. P. Jackson, and T. Kouzarides, Nature 382:88-90, 1996). This regulation involves interaction with TFIIIB, a multisubunit factor that is required for the expression of all Pol III templates (C. G. C. Larminie, C. A. Cairns, R. Mital, K. Martin, T. Kouzarides, S. P. Jackson, and R. J. White, EMBO J. 16:2061-2071, 1997; W.-M. Chu, Z. Wang, R. G. Roeder, and C. W. Schmid, J. Biol. Chem. 272:14755-14761, 1997). However, it has not been established why RB binding to TFIIIB results in transcriptional repression. For several Pol II-transcribed genes, RB has been shown to inhibit expression by recruiting histone deacetylases, which are thought to decrease promoter accessibility. We present evidence that histone deacetylases exert a negative effect on Pol III activity in vivo. However, RB remains able to regulate Pol III transcription in the presence of the histone deacetylase inhibitor trichostatin A. Instead, RB represses by disrupting interactions between TFIIIB and other components of the basal Pol III transcription apparatus. Recruitment of TFIIIB to most class III genes requires its binding to TFIIIC2, but this can be blocked by RB. In addition, RB disrupts the interaction between TFIIIB and Pol III that is essential for transcription. The ability of RB to inhibit these key interactions can explain its action as a potent repressor of class III gene expression.

MeSH Terms
Animals Cell Line Enzyme Inhibitors/pharmacology Histone Deacetylase Inhibitors Histone Deacetylases/metabolism Humans Hydroxamic Acids/pharmacology Mice Models, Genetic Precipitin Tests Promoter Regions, Genetic RNA Polymerase III/genetics,metabolism RNA, Small Nuclear/genetics,metabolism Recombinant Fusion Proteins/metabolism Retinoblastoma Protein/genetics,metabolism Transcription Factor TFIIIB Transcription Factors/genetics,metabolism Transcription Factors, TFIII/metabolism Transcription, Genetic/genetics Transfection
Chemicals
Enzyme Inhibitors Histone Deacetylase Inhibitors Hydroxamic Acids RNA, Small Nuclear Recombinant Fusion Proteins Retinoblastoma Protein Transcription Factor TFIIIB Transcription Factors Transcription Factors, TFIII U6 small nuclear RNA transcription factor TFIIIC trichostatin A RNA Polymerase III Histone Deacetylases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sutcliffe J E
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Brown T R
Allison S J
Scott P H
White R J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.24.9192-9202.2000
Published
2000-12-00
Pages
9192-202
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC102177
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1128/MCB.20.24.9192-9202.2000 PMC Full Text View journal details
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