Abascal-Palacios, G.
Ramsay, E.P.
Beuron, F.
Morris, E.
Vannini, A.
(2018). Structural basis of RNA polymerase III transcription initiation. Nature,
Vol.553
(7688),
pp. 301-306.
show abstract
RNA polymerase (Pol) III transcribes essential non-coding RNAs, including the entire pool of transfer RNAs, the 5S ribosomal RNA and the U6 spliceosomal RNA, and is often deregulated in cancer cells. The initiation of gene transcription by Pol III requires the activity of the transcription factor TFIIIB to form a transcriptionally active Pol III preinitiation complex (PIC). Here we present electron microscopy reconstructions of Pol III PICs at 3.4-4.0 Å and a reconstruction of unbound apo-Pol III at 3.1 Å. TFIIIB fully encircles the DNA and restructures Pol III. In particular, binding of the TFIIIB subunit Bdp1 rearranges the Pol III-specific subunits C37 and C34, thereby promoting DNA opening. The unwound DNA directly contacts both sides of the Pol III cleft. Topologically, the Pol III PIC resembles the Pol II PIC, whereas the Pol I PIC is more divergent. The structures presented unravel the molecular mechanisms underlying the first steps of Pol III transcription and also the general conserved mechanisms of gene transcription initiation..
Gouge, J.
Satia, K.
Guthertz, N.
Widya, M.
Thompson, A.J.
Cousin, P.
Dergai, O.
Hernandez, N.
Vannini, A.
(2015). Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2. Cell,
Vol.163
(6),
pp. 1375-1387.
show abstract
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..
Vannini, A.
(2013). A structural perspective on RNA polymerase I and RNA polymerase III transcription machineries. Biochim biophys acta,
Vol.1829
(3-4),
pp. 258-264.
show abstract
RNA polymerase I and III are responsible for the bulk of nuclear transcription in actively growing cells and their activity impacts the cellular biosynthetic capacity. As a consequence, RNA polymerase I and III deregulation has been directly linked to cancer development. The complexity of RNA polymerase I and III transcription apparatuses has hampered their structural characterization. However, in the last decade tremendous progresses have been made, providing insights into the molecular and functional architecture of these multi-subunit transcriptional machineries. Here we summarize the available structural data on RNA polymerase I and III, including specific transcription factors and global regulators. Despite the overall scarcity of detailed structural data, the recent advances in the structural biology of RNA polymerase I and III represent the first step towards a comprehensive understanding of the molecular mechanism underlying RNA polymerase I and III transcription. This article is part of a Special Issue entitled: Transcription by Odd Pols..
Vannini, A.
Cramer, P.
(2012). Conservation between the RNA polymerase I, II, and III transcription initiation machineries. Mol cell,
Vol.45
(4),
pp. 439-446.
show abstract
Recent studies of the three eukaryotic transcription machineries revealed that all initiation complexes share a conserved core. This core consists of the RNA polymerase (I, II, or III), the TATA box-binding protein (TBP), and transcription factors TFIIB, TFIIE, and TFIIF (for Pol II) or proteins structurally and functionally related to parts of these factors (for Pol I and Pol III). The conserved core initiation complex stabilizes the open DNA promoter complex and directs initial RNA synthesis. The periphery of the core initiation complex is decorated by additional polymerase-specific factors that account for functional differences in promoter recognition and opening, and gene class-specific regulation. This review outlines the similarities and differences between these important molecular machines..
Vannini, A.
Ringel, R.
Kusser, A.G.
Berninghausen, O.
Kassavetis, G.A.
Cramer, P.
(2010). Molecular Basis of RNA Polymerase III Transcription Repression by Maf1. Cell,
Vol.143
(1),
pp. 59-70.
Cramer, P.
Armache, K.-.
Baumli, S.
Benkert, S.
Brueckner, E.
Buchen, C.
Damsma, G.E.
Dengl, S.
Geiger, S.R.
Jaslak, A.J.
Jawhari, A.
Jennebach, S.
Kamenski, T.
Kettenberger, H.
Kuhn, C.-.
Lehmann, E.
Leike, K.
Sydow, J.E.
Vannini, A.
(2008). Structure of eukaryotic RNA polymerases. Annual review of biophysics,
Vol.37,
pp. 337-352.
Vannini, A.
Volpari, C.
Gallinari, P.
Jones, P.
Mattu, M.
Carfi, A.
De Francesco, R.
Steinkuehler, C.
Di Marco, S.
(2007). Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex. Embo reports,
Vol.8
(9),
pp. 879-884.
Lorenzen, K.
Vannini, A.
Crarner, P.
Heck, A.J.
(2007). Structural biology of RNA polymerase III: Mass spectrometry elucidates subcomplex architecture. Structure,
Vol.15
(10),
pp. 1237-1245.
Vannini, A.
Volpari, C.
Filocamo, G.
Casavola, E.C.
Brunetti, M.
Renzoni, D.
Chakravarty, P.
Paolini, C.
De Francesco, R.
Gallinari, P.
Steinkuhler, C.
Di Marco, S.
(2004). Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proceedings of the national academy of sciences of the united states of america,
Vol.101
(42),
pp. 15064-15069.
Vannini, A.
Volpari, C.
Gargioli, C.
Muraglia, E.
Cortese, R.
De Francesco, R.
Neddermann, P.
Di Marco, S.
(2002). The crystal structure of the quorum sensing protein TraR bound to its autoinducer and target DNA. Embo journal,
Vol.21
(17),
pp. 4393-4401.