Nuclear regulation and stress
CEA Saclay/Bât. 144
Tél: 01 69 08 37 96 ou 59 57
christine.conesa@cea.fr / olivier.lefebvre@cea.fr
iBiTec-S /SBIGeM / LREGE
Human resources
Joël ACKER, Researcher
Christine CONESA, Group Leader
Olivier LEFEBVRE, Group Leader
Marie VANDAMME, Research Technician
Cyril SAGUEZ, Postdoctoral Fellow
Adeline VEILLET, Postdoctoral Fellow
Ngoc Thuy Trinh NGUYEN, PhD Student
Research Programs
The group is interested in gene expression regulation in yeast of genes transcribed by RNA polymerase III in response to various stresses. We are targeting the identification of networks involved in modulating transcriptional activity, from signal perception to components of the transcription machinery. In particular, we are working in three main directions. The first theme is the functional identification and characterization of proteins involved in regulatory cascades. We have characterized Maf1, the first negative regulator of Pol III transcription (Oficjalska-Pham Molecular Cell 2006). The second is dedicated to the in-depth characterization of those molecular mechanisms that allow a cell to adapt its level of transcription to environmental conditions. We have recently published, in collaboration with a laboratory from EMBL Grenoble, the first crystallographic structure of 2 subunits of TFIIIC, a Pol III transcription factor (Mylona Molecular Cell 2006). Our third research theme extends in silico the phylogenomic analysis of regulatory networks to all Hemiascomycetes yeast (Marck Nucleic Acids Research 2006).
© CEA/O. Lefebvre
Maf1 dephosphorylation is the signal for:
• Maf1 nuclear entry
• Increased Maf1-Pol III interaction
• Transcriptional repression
Key words
Transcription, regulation, RNA, Pol III, stress, biochemistry, functional genomics, chromatin immunoprecipitation, DNA chips, RNomics
Publications
Conesa C, Acker J. (2010). Sub1/PC4 a chromatin associated protein with multiple functions in transcription. RNA Biol. 7, 287-290.
Gajda A, Towpik J, Steuerwald U, Muller C W, Lefebvre O, Boguta M. (2010). Full Repression of RNA Polymerase III Transcription Requires Interaction between Two Domains of Its Negative Regulator Maf1. J Biol Chem. 285, 35719-35727.
Grosjean H, de Crécy-Lagard V, Marck C. (2010). Deciphering synonymous codons in the three domains of life: co-evolution with specific tRNA modification enzymes. FEBS Lett., 584, 252-254.
Payen C, Fischer G, Marck C, Proux C, Sherman DJ, Coppée JY, Johnston M, Dujon B, Neuvéglise C. (2009). Unusual composition of yeast chromosome arm is associated with its delayed replication. Genome Res., 19, 1710-1721.
Tavenet A, Suleau A, Dubreuil G, Ferrari R, Ducrot C, Michaut M, Aude J C, Dieci G, Lefebvre O, Conesa C, Acker J. (2009). Genome-wide location analysis reveals a role for Sub1 in RNA polymerase III transcription. Proc Natl Acad Sci U S A. 106, 14265-14270.
Acker J, Ozanne C, Kachouri-Lafond R, Gaillardin C, Neuvéglise C, Marck C. (2008). Dicistronic tRNA–5S rRNA genes in Yarrowia lipolytica: an alternative TFIIIA-independent way for expression of 5S rRNA genes. Nucleic Acids Res. 36, 5832-44.
Goodfellow SJ, Graham EL, Kantidakis T, Marshall L, Coppins BA, Oficjalska-Pham D, Gérard M, Lefebvre O, White RJ. (2008). Regulation of RNA Polymerase III Transcription by Maf1 in Mammalian Cells. J Mol Biol. 378, 481-91.
Souciet JL, Dujon B, Gaillardin C, Johnston M, Baret PV, Cliften P, Sherman DJ, Weissenbach J, Westhof E, Wincker P, Jubin C, Poulain J, Barbe V, Segurence B, Artiguenave F, Anthouard V, Vacherie B, Val ME, Fulton RS, Minx P, Wilson R, Durrens P, Jean G, Marck C, Martin T, Nikolski M, Rolland T, Seret ML, Casaregola S, Despons L, Fairhead C, Fischer G, Lafontaine I, Leh V, Lemaire M, De Montigny J, Neuveglise C, Thierry A, Blanc-Lenfle I, Bleykasten C, Diffels J, Fritsch E, Frangeul L, Goeffon A, Jauniaux N, Kachouri-Lafond R, Payen C, Potier S, Pribylova L, Ozanne C, Richard GF, Sacerdot C, Straub ML, Talla E. (2009). Comparative genomics of protoploid Saccharomycetaceae. Genome Res. 19, 1696-709.
Grosjean H, Marck C, Gaspin C, Decatur WA, de Crecy-Lagard V. (2008). RNomics and Modomics in the halophilic archaea Haloferax volcanii: identification of RNA modification genes. BMC Genomics. 9, 470.
Towpik J, Graczyk D, Gajda A, Lefebvre O, Boguta M. (2008). Derepression of RNA polymerase III transcription by phosphorylation and nuclear export of its negative regulator, Maf1. J Biol Chem. 283, 17168-74.
Ciesla M, Towpik J, Graczyk D, Oficjalska-Pham D, Harismendy O, Suleau A, Balicki K, Conesa C, Lefebvre O, Boguta M. (2007). Maf1 is involved in coupling carbon metabolism to RNA Polymerase III transcription. Mol Cell Biol. 27, 7693-702.
de Crécy-Lagard V, Marck C, Brochier-Armanet C, Grosjean H. (2007).Comparative RNomics and Modomics in Mollicutes: Prediction of Gene Function and Evolutionary Implications. IUBMB Life. 59: 634 - 658.
Dumay-Odelot H, Marck C, Durrieu-Gaillard S, Lefebvre O, Jourdain S, Prochazkova M, Pflieger A, Teichmann, M. (2007). Identification, molecular cloning and characterization of the sixth subunit of human transcription factor TFIIIC. J Biol Chem. 282, 17179-17189.
Grosjean H, Marck C, de Crécy-Lagard V. (2007).The various strategies of codon decoding in organisms of the three domains of life: evolutionary implications. Nucleic Acids Symp Ser (Oxf). 51, 15-16.
Mylona A, Fernández-Tornero C, Legrand P, Sentenac A, Acker J, Müller CW. (2006). Structure of the tau60/Delta tau91 subcomplex of yeast transcription factor IIIC: insights into preinitiation complex assembly. Mol Cell. 24, 221-322.
Oficjalska-Pham D, Harismendy O, Smagowicz W, Gonzalez de Peredo A, Boguta M, Sentenac A, Lefebvre O. (2006). General repression of RNA polymerase III transcription is triggered by protein phosphatase type 2A-mediated dephosphorylation of Maf1. Mol Cell. 22, 623-632.
Soutourina J, Bordas-Le Floch V, Gendrel G, Flores A, Ducrot C, Dumay-Odelot H, Soularue P, Navarro F, Cairns BR, Lefebvre O, Werner M. (2006). Rsc4 connects the chromatin remodeler RSC to RNA polymerases. Mol Cell Biol. 26, 4920-4933.
Ducrot C, Lefebvre O, Landrieux E, Guirouilh-Barbat J, Sentenac A, Acker J. (2006). Reconstitution of the Yeast RNA Polymerase III Transcription System with All Recombinant Factors. J Biol Chem. 281, 11685-11692.
Marck C, Kachouri-Lafond R, Lafontaine I, Westhof E, Dujon B, Grosjean H. (2006). The RNA polymerase III-dependent family of genes in hemiascomycetes: comparative RNomics, decoding strategies, transcription and evolutionary implications. Nucleic Acids Res. 34, 1816-1835.
Mylona A, Acker J, Fernandez-Tornero C, Sentenac A, Muller CW. (2006). Expression, proteolytic analysis, reconstitution, and crystallization of the tau60/tau91 subcomplex of yeast TFIIIC. Protein Expr Purif. 45, 255-261.
Landrieux E, Alic N, Ducrot C, Acker J, Riva M, Carles C. (2006). A subcomplex of RNA polymerase III subunits involved in transcription termination and reinitiation. EMBO J. 25, 118-128.
Conesa C, Ruotolo R, Soularue P, Simms TA, Donze D, Sentenac A, Dieci G. (2005). Modulation of yeast genome expression in response to defective RNA polymerase III-dependent transcription. Mol Cell Biol. 25, 8631-8642.
Dujon B, Sherman D, Fischer G, Durrens P, Casaregola S, Lafontaine I, De Montigny J, Marck C, Neuveglise C, Talla E, Goffard N, Frangeul L, Aigle M, Anthouard V, Babour A, Barbe V, Barnay S, Blanchin S, Beckerich JM, Beyne E, Bleykasten C, Boisrame A, Boyer J, Cattolico L, Confanioleri F, De Daruvar A, Despons L, Fabre E, Fairhead C, Ferry-Dumazet H, Groppi A, Hantraye F, Hennequin C, Jauniaux N, Joyet P, Kachouri R, Kerrest A, Koszul R, Lemaire M, Lesur I, Ma L, Muller H, Nicaud JM, Nikolski M, Oztas S, Ozier-Kalogeropoulos O, Pellenz S, Potier S, Richard GF, Straub ML, Suleau A, Swennen D, Tekaia F, Wesolowski-Louvel M, Westhof E, Wirth B, Zeniou-Meyer M, Zivanovic I, Bolotin-Fukuhara M, Thierry A, Bouchier C, Caudron B, Scarpelli C, Gaillardin C, Weissenbach J, Wincker P, Souciet JL. (2004). Genome evolution in yeasts. Nature. 430, 35-44.
Harismendy O, Gendrel CG, Soularue P, Gidrol X, Sentenac A, Werner M, Lefebvre O. (2003). Genome-wide location of yeast RNA polymerase III transcription machinery. EMBO J. 22, 4738-4747.
Jourdain S, Acker J, Ducrot C, Sentenac A, Lefebvre O. (2003). The tau95 subunit of yeast TFIIIC influences upstream and downstream functions of TFIIIC.DNA complexes. J Biol Chem. 278, 10450-10457.
Marck C, Grosjean H. (2003). Identification of BHB splicing motifs in intron-containing tRNAs from 18 archaea: evolutionary implications. RNA. 9, 1516-1531.
Siaut M, Zaros C, Levivier E, Ferri ML, Court M, Werner M, Callebaut I, Thuriaux P, Sentenac A, Conesa C. (2003). An Rpb4/Rpb7-like complex in yeast RNA polymerase III contains the orthologue of mammalian CGRP-RCP. Mol Cell Biol. 23, 195-205.
Dumay-Odelot H, Acker J, Arrebola R, Sentenac A, Marck C. (2002). Multiple roles of the tau131 subunit of yeast transcription factor IIIC (TFIIIC) in TFIIIB assembly. Mol Cell Biol. 22, 298-308.
Marck C, Grosjean H. (2002). tRNomics: analysis of tRNA genes from 50 genomes of Eukarya, Archaea, and Bacteria reveals anticodon-sparing strategies and domain-specific features. RNA. 8, 1189-1232.
Pluta K, Lefebvre O, Martin NC, Smagowicz WJ, Stanford DR, Ellis SR, Hopper AK, Sentenac A, Boguta M. (2001). Maf1p, a negative effector of RNA polymerase III in Saccharomyces cerevisiae. Mol Cell Biol. 21, 5031-5040.
Main collaborations
Magdalena BOGUTA, IBB, Warsaw, Poland:
Cristoph MÜLLER, EMBL Heidelberg, Germany
Martin TEICHMANN, IECB/INSERM, Pessac, France
Bernard DUJON, Institut Pasteur, France
Claude GAILLARDIN, INRA Paris-Grignon, France
Eric WESTHOF, IBMC Strasbourg, France