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Gene Review

BRF1  -  Brf1p

Saccharomyces cerevisiae S288c

Synonyms: B-related factor 1, BRF-1, PCF4, TDS4, TFIIIB, ...
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Disease relevance of BRF1

  • Mammalian TFIIIB can be separated into two fractions required for transcription of the adenovirus type 2 VAI gene, which have been designated 0.38M-TFIIIB and 0.48M-TFIIIB [1].

High impact information on BRF1

  • CK2 associates with and normally activates the TATA binding protein (TBP) subunit of TFIIIB [2].
  • Here we report that RNA polymerase (pol) III transcription is repressed in response to DNA damage by downregulation of TFIIIB, the core component of the pol III transcriptional machinery [2].
  • A dominant mutation in the PCF4 gene of S. cerevisiae was isolated as a suppressor of a tRNA gene A block promoter mutation [3].
  • The TFIIIB-dependent binding of pol III to the SUP4 tRNA and 5S rRNA genes has been analyzed in binary (protein and DNA only) and precisely arrested ternary (protein, DNA, and RNA) transcription complexes [4].
  • Thus, TFIIIB is the sole transcription initiation factor of S. cerevisiae pol III; TFIIIC and TFIIIA are assembly factors for TFIIIB [4].

Biological context of BRF1

  • Deletion of sequences at either the amino or carboxyl terminus of BRF1 gave both temperature- and cold-sensitive phenotypes [5].
  • Our results suggest that the binding sites for BRF1 and TFIIIB90 on TBP-DNA both overlap the binding sites for TFIIA and TFIIB [6].
  • Analysis of a 17.9 kb region from Saccharomyces cerevisiae chromosome VII reveals the presence of eight open reading frames, including BRF1 (TFIIIB70) and GCN5 genes [7].
  • The Saccharomyces cerevisiae RNA polymerase III recruitment factor subunits Brf1 and Bdp1 impose a strict sequence preference for the downstream half of the TATA box [8].
  • Using quantitative reverse transcription-polymerase chain reaction, 14-3-3 beta and BRF1 were found to be coexpressed in four different human tissues, suggesting a biologic role for their interaction in the regulation of cRaf-1-mediated signal transduction processes [9].

Associations of BRF1 with chemical compounds


Physical interactions of BRF1

  • Finally, we demonstrate that BRF but not TFIIB binds the Pol III subunit C34 and we define a region of C34 necessary for this interaction [14].
  • Transcription factor (TF) IIIB, the central transcription initiation factor of RNA polymerase III (pol III), is composed of three subunits, Bdp1, Brf1 and TATA-binding protein (TBP), all essential for normal function in vivo and in vitro [15].
  • Dominant mutations in the ligand binding channel of the first TPR array, TPRs1-5, and on the back side of this array, increase Brf1 binding by Tfc4 [16].
  • A promoter-deficient U6 RNA gene harboring GAL4-binding sites could be reactivated by fusing the GAL4 DNA-binding domain to components of the general transcription factor TFIIIC (tau) or TFIIIB [17].
  • GCN4 effectively blocks initiation of transcription only when prebound to sites that overlap with the binding site of TFIIIB [18].

Regulatory relationships of BRF1

  • Furthermore, TBP mutations that selectively inhibit Pol III transcription in vivo impair interactions between TBP and the BRF carboxy-terminal domain [14].

Other interactions of BRF1

  • By assaying for interactions between BRF and other Pol III transcription factors, we show that it is able to bind to the 135-kD subunit of TFIIIC and also to TBP [14].
  • Essential roles of Bdp1, a subunit of RNA polymerase III initiation factor TFIIIB, in transcription and tRNA processing [19].
  • The interaction of yeast TFIIIB with the region upstream of the SUP4 tRNATyr gene was extensively probed by use of photoreactive phosphodiesters, deoxyuridines, and deoxycytidines that are site specifically incorporated into DNA [20].
  • The sequence includes the BRF1 gene, encoding TFIIIB70, the 5' portion of the GCN5 gene, an open reading frame (ORF) previously identified as ORF MGA1, whose translation product shows similarity to heat-shock transcription factors and five new ORFs [7].
  • Tfc4 contains two arrays of tetratricopeptide repeats (TPRs), each of which provides a binding site for Brf1 [16].

Analytical, diagnostic and therapeutic context of BRF1

  • The individual TFIIIB subunits are nuclear by immunofluorescence and are calculated to have nuclear concentrations in the low micromolar range [21].
  • This orientation of yeast TBP in Pol III promoter-bound TFIIIB is the same as in Pol II promoter-bound TFIID and in TBP-DNA complexes that have been analyzed by X-ray crystallography [22].
  • To define the Pol III transcriptome in Saccharomyces cerevisiae, we performed genome-wide chromatin immunoprecipitation using subunits of Pol III, TFIIIB and TFIIIC [23].
  • These findings together with the results from site-directed mutagenesis support the hypothesis that gain-of-function mutations at amino acid 190 in TPR2 stabilize an alternative conformation of TFIIIC131 that promotes its interaction with Brf1 [24].
  • Additionally, biochemical fractionation of wild-type and mutant cell extracts shows that PCF1-1 increases the amount of the 70-kDa TFIIIB subunit detectable by Western (immunoblot) analysis in purified TFIIIB fractions and the transcription activity of a TFIIIB" fraction containing the 90-kDa subunit of this factor [25].


  1. RNA polymerase III transcription from the human U6 and adenovirus type 2 VAI promoters has different requirements for human BRF, a subunit of human TFIIIB. Mital, R., Kobayashi, R., Hernandez, N. Mol. Cell. Biol. (1996) [Pubmed]
  2. TATA binding protein-associated CK2 transduces DNA damage signals to the RNA polymerase III transcriptional machinery. Ghavidel, A., Schultz, M.C. Cell (2001) [Pubmed]
  3. PCF4 encodes an RNA polymerase III transcription factor with homology to TFIIB. López-De-León, A., Librizzi, M., Puglia, K., Willis, I.M. Cell (1992) [Pubmed]
  4. S. cerevisiae TFIIIB is the transcription initiation factor proper of RNA polymerase III, while TFIIIA and TFIIIC are assembly factors. Kassavetis, G.A., Braun, B.R., Nguyen, L.H., Geiduschek, E.P. Cell (1990) [Pubmed]
  5. A yeast TFIIB-related factor involved in RNA polymerase III transcription. Colbert, T., Hahn, S. Genes Dev. (1992) [Pubmed]
  6. Cloning and functional characterization of the gene encoding the TFIIIB90 subunit of RNA polymerase III transcription factor TFIIIB. Roberts, S., Miller, S.J., Lane, W.S., Lee, S., Hahn, S. J. Biol. Chem. (1996) [Pubmed]
  7. Analysis of a 17.9 kb region from Saccharomyces cerevisiae chromosome VII reveals the presence of eight open reading frames, including BRF1 (TFIIIB70) and GCN5 genes. Feroli, F., Carignani, G., Pavanello, A., Guerreiro, P., Azevedo, D., Rodrigues-Pousada, C., Melchioretto, P., Panzeri, L., Agostoni Carbone, M.L. Yeast (1997) [Pubmed]
  8. The Saccharomyces cerevisiae RNA polymerase III recruitment factor subunits Brf1 and Bdp1 impose a strict sequence preference for the downstream half of the TATA box. Tsihlis, N.D., Grove, A. Nucleic Acids Res. (2006) [Pubmed]
  9. The product of the primary response gene BRF1 inhibits the interaction between 14-3-3 proteins and cRaf-1 in the yeast trihybrid system. Bustin, S.A., McKay, I.A. DNA Cell Biol. (1999) [Pubmed]
  10. The role of the TATA-binding protein in the assembly and function of the multisubunit yeast RNA polymerase III transcription factor, TFIIIB. Kassavetis, G.A., Joazeiro, C.A., Pisano, M., Geiduschek, E.P., Colbert, T., Hahn, S., Blanco, J.A. Cell (1992) [Pubmed]
  11. TATA-box DNA binding activity and subunit composition for RNA polymerase III transcription factor IIIB from Xenopus laevis. McBryant, S.J., Meier, E., Leresche, A., Sharp, S.J., Wolf, V.J., Gottesfeld, J.M. Mol. Cell. Biol. (1996) [Pubmed]
  12. Selective inactivation of two components of the multiprotein transcription factor TFIIIB in cycloheximide growth-arrested yeast cells. Dieci, G., Duimio, L., Peracchia, G., Ottonello, S. J. Biol. Chem. (1995) [Pubmed]
  13. Two steps in Maf1-dependent repression of transcription by RNA polymerase III. Desai, N., Lee, J., Upadhya, R., Chu, Y., Moir, R.D., Willis, I.M. J. Biol. Chem. (2005) [Pubmed]
  14. Conserved functional domains of the RNA polymerase III general transcription factor BRF. Khoo, B., Brophy, B., Jackson, S.P. Genes Dev. (1994) [Pubmed]
  15. Reconfiguring the connectivity of a multiprotein complex: fusions of yeast TATA-binding protein with Brf1, and the function of transcription factor IIIB. Kassavetis, G.A., Soragni, E., Driscoll, R., Geiduschek, E.P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  16. The Brf1 and Bdp1 subunits of transcription factor TFIIIB bind to overlapping sites in the tetratricopeptide repeats of Tfc4. Liao, Y., Willis, I.M., Moir, R.D. J. Biol. Chem. (2003) [Pubmed]
  17. Directing transcription of an RNA polymerase III gene via GAL4 sites. Marsolier, M.C., Chaussivert, N., Lefebvre, O., Conesa, C., Werner, M., Sentenac, A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  18. Repression and redirection of Saccharomyces cerevisiae tRNA synthesis from upstream of the transcriptional start site. Léveillard, T., Kassavetis, G.A., Geiduschek, E.P. J. Biol. Chem. (1993) [Pubmed]
  19. Essential roles of Bdp1, a subunit of RNA polymerase III initiation factor TFIIIB, in transcription and tRNA processing. Ishiguro, A., Kassavetis, G.A., Geiduschek, E.P. Mol. Cell. Biol. (2002) [Pubmed]
  20. Spatial organization of the core region of yeast TFIIIB-DNA complexes. Persinger, J., Sengupta, S.M., Bartholomew, B. Mol. Cell. Biol. (1999) [Pubmed]
  21. A differential response of wild type and mutant promoters to TFIIIB70 overexpression in vivo and in vitro. Sethy-Coraci, I., Moir, R.D., López-de-León, A., Willis, I.M. Nucleic Acids Res. (1998) [Pubmed]
  22. The symmetry of the yeast U6 RNA gene's TATA box and the orientation of the TATA-binding protein in yeast TFIIIB. Whitehall, S.K., Kassavetis, G.A., Geiduschek, E.P. Genes Dev. (1995) [Pubmed]
  23. The RNA polymerase III transcriptome revealed by genome-wide localization and activity-occupancy relationships. Roberts, D.N., Stewart, A.J., Huff, J.T., Cairns, B.R. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  24. A gain-of-function mutation in the second tetratricopeptide repeat of TFIIIC131 relieves autoinhibition of Brf1 binding. Moir, R.D., Puglia, K.V., Willis, I.M. Mol. Cell. Biol. (2002) [Pubmed]
  25. A mutation in the second largest subunit of TFIIIC increases a rate-limiting step in transcription by RNA polymerase III. Rameau, G., Puglia, K., Crowe, A., Sethy, I., Willis, I. Mol. Cell. Biol. (1994) [Pubmed]
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