| Structural highlights
Disease
[TBP_HUMAN] Defects in TBP are the cause of spinocerebellar ataxia type 17 (SCA17) [MIM:607136]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA17 is an autosomal dominant cerebellar ataxia (ADCA) characterized by widespread cerebral and cerebellar atrophy, dementia and extrapyramidal signs. The molecular defect in SCA17 is the expansion of a CAG repeat in the coding region of TBP. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.[1] [2] [3]
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.[4] [5] [6] [BDP1_HUMAN] General activator of RNA polymerase III transcription. Requires for transcription from all three types of polymerase III promoters. Requires for transcription of genes with internal promoter elements and with promoter elements upstream of the initiation site.[7] [TBP_HUMAN] General transcription factor that functions at the core of the DNA-binding multiprotein factor TFIID. Binding of TFIID to the TATA box is the initial transcriptional step of the pre-initiation complex (PIC), playing a role in the activation of eukaryotic genes transcribed by RNA polymerase II. Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1 with the rDNA promoter. SL1 is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA.[8]
Publication Abstract from PubMed
Initiation of gene transcription by RNA polymerase (Pol) III requires the activity of TFIIIB, a complex formed by Brf1 (or Brf2), TBP (TATA-binding protein), and Bdp1. TFIIIB is required for recruitment of Pol III and to promote the transition from a closed to an open Pol III pre-initiation complex, a process dependent on the activity of the Bdp1 subunit. Here, we present a crystal structure of a Brf2-TBP-Bdp1 complex bound to DNA at 2.7 A resolution, integrated with single-molecule FRET analysis and in vitro biochemical assays. Our study provides a structural insight on how Bdp1 is assembled into TFIIIB complexes, reveals structural and functional similarities between Bdp1 and Pol II factors TFIIA and TFIIF, and unravels essential interactions with DNA and with the upstream factor SNAPc. Furthermore, our data support the idea of a concerted mechanism involving TFIIIB and RNA polymerase III subunits for the closed to open pre-initiation complex transition.Transcription initiation by RNA polymerase III requires TFIIIB, a complex formed by Brf1/Brf2, TBP and Bdp1. Here, the authors describe the crystal structure of a Brf2-TBP-Bdp1 complex bound to a DNA promoter and characterize the role of Bdp1 in TFIIIB assembly and pre-initiation complex formation.
Molecular mechanisms of Bdp1 in TFIIIB assembly and RNA polymerase III transcription initiation.,Gouge J, Guthertz N, Kramm K, Dergai O, Abascal-Palacios G, Satia K, Cousin P, Hernandez N, Grohmann D, Vannini A Nat Commun. 2017 Jul 25;8(1):130. doi: 10.1038/s41467-017-00126-1. PMID:28743884[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zuhlke C, Hellenbroich Y, Dalski A, Kononowa N, Hagenah J, Vieregge P, Riess O, Klein C, Schwinger E. Different types of repeat expansion in the TATA-binding protein gene are associated with a new form of inherited ataxia. Eur J Hum Genet. 2001 Mar;9(3):160-4. PMID:11313753 doi:10.1038/sj.ejhg.5200617
- ↑ Nakamura K, Jeong SY, Uchihara T, Anno M, Nagashima K, Nagashima T, Ikeda S, Tsuji S, Kanazawa I. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet. 2001 Jul 1;10(14):1441-8. PMID:11448935
- ↑ Silveira I, Miranda C, Guimaraes L, Moreira MC, Alonso I, Mendonca P, Ferro A, Pinto-Basto J, Coelho J, Ferreirinha F, Poirier J, Parreira E, Vale J, Januario C, Barbot C, Tuna A, Barros J, Koide R, Tsuji S, Holmes SE, Margolis RL, Jardim L, Pandolfo M, Coutinho P, Sequeiros J. Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. Arch Neurol. 2002 Apr;59(4):623-9. PMID:11939898
- ↑ 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
- ↑ 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
- ↑ Friedrich JK, Panov KI, Cabart P, Russell J, Zomerdijk JC. TBP-TAF complex SL1 directs RNA polymerase I pre-initiation complex formation and stabilizes upstream binding factor at the rDNA promoter. J Biol Chem. 2005 Aug 19;280(33):29551-8. Epub 2005 Jun 21. PMID:15970593 doi:10.1074/jbc.M501595200
- ↑ Gouge J, Guthertz N, Kramm K, Dergai O, Abascal-Palacios G, Satia K, Cousin P, Hernandez N, Grohmann D, Vannini A. Molecular mechanisms of Bdp1 in TFIIIB assembly and RNA polymerase III transcription initiation. Nat Commun. 2017 Jul 25;8(1):130. doi: 10.1038/s41467-017-00126-1. PMID:28743884 doi:http://dx.doi.org/10.1038/s41467-017-00126-1
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