Structural highlights
Function
BRF2_HUMAN General activator of RNA polymerase III transcription. Factor exclusively required for RNA polymerase III transcription of genes with promoter elements upstream of the initiation sites.[1] [2] [3]
Publication Abstract from PubMed
TFIIB-related factor 2 (Brf2) is a member of the family of TFIIB-like core transcription factors. Brf2 recruits RNA polymerase (Pol) III to type III gene-external promoters, including the U6 spliceosomal RNA and selenocysteine tRNA genes. Found only in vertebrates, Brf2 has been linked to tumorigenesis but the underlying mechanisms remain elusive. We have solved crystal structures of a human Brf2-TBP complex bound to natural promoters, obtaining a detailed view of the molecular interactions occurring at Brf2-dependent Pol III promoters and highlighting the general structural and functional conservation of human Pol II and Pol III pre-initiation complexes. Surprisingly, our structural and functional studies unravel a Brf2 redox-sensing module capable of specifically regulating Pol III transcriptional output in living cells. Furthermore, we establish Brf2 as a central redox-sensing transcription factor involved in the oxidative stress pathway and provide a mechanistic model for Brf2 genetic activation in lung and breast cancer.
Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2.,Gouge J, Satia K, Guthertz N, Widya M, Thompson AJ, Cousin P, Dergai O, Hernandez N, Vannini A Cell. 2015 Dec 3;163(6):1375-87. doi: 10.1016/j.cell.2015.11.005. PMID:26638071[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schramm L, Pendergrast PS, Sun Y, Hernandez N. Different human TFIIIB activities direct RNA polymerase III transcription from TATA-containing and TATA-less promoters. Genes Dev. 2000 Oct 15;14(20):2650-63. PMID:11040218
- ↑ Teichmann M, Wang Z, Roeder RG. A stable complex of a novel transcription factor IIB- related factor, human TFIIIB50, and associated proteins mediate selective transcription by RNA polymerase III of genes with upstream promoter elements. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14200-5. PMID:11121026 doi:http://dx.doi.org/10.1073/pnas.97.26.14200
- ↑ Cabart P, Murphy S. BRFU, a TFIIB-like factor, is directly recruited to the TATA-box of polymerase III small nuclear RNA gene promoters through its interaction with TATA-binding protein. J Biol Chem. 2001 Nov 16;276(46):43056-64. Epub 2001 Sep 19. PMID:11564744 doi:http://dx.doi.org/10.1074/jbc.M108515200
- ↑ Gouge J, Satia K, Guthertz N, Widya M, Thompson AJ, Cousin P, Dergai O, Hernandez N, Vannini A. Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2. Cell. 2015 Dec 3;163(6):1375-87. doi: 10.1016/j.cell.2015.11.005. PMID:26638071 doi:http://dx.doi.org/10.1016/j.cell.2015.11.005
