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Mechanistic analysis of RNA polymerase III regulation by the retinoblastoma protein
Author(s) -
Larminie Christopher G. C.,
Cairns Carol A.,
Mital Renu,
Martin Klaus,
Kouzarides Tony,
Jackson Stephen P.,
White Robert J.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.8.2061
Subject(s) - rna polymerase iii , biology , transcription (linguistics) , rna polymerase ii , microbiology and biotechnology , tata box binding protein , transcription factor , rna polymerase , dna binding protein , rna , genetics , promoter , gene , gene expression , linguistics , philosophy
The tumour suppressor protein RB restricts cellular growth. This may involve inhibiting the synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III. We have shown previously that RB can repress pol III transcription when overexpressed either in vitro or in vivo . We also demonstrated that pol III activity is elevated substantially in primary fibroblasts from RB‐deficient mice. Here we address the molecular mechanism of this regulation. RB is shown to repress all types of pol III promoter. It can do this even if added after transcription complex assembly. Functional assays demonstrate that RB targets specifically the general pol III factor TFIIIB. A physical interaction between TFIIIB and RB is indicated by fractionation, pull‐down and immunoprecipitation data. We show that TFIIIB activity is elevated in primary fibroblasts from RB‐deficient mice. TFIIIB is a multisubunit complex that includes the TATA‐binding protein (TBP) and a TFIIB‐related factor called BRF. We show that RB itself contains regions of homology to both TBP and BRF and propose a model in which RB disrupts TFIIIB by mimicking these two components.