CGM - Department Genes Expressions
mRNA metabolism in eucaryotes
Group leader: Joëlle MARIE
Last update: 10-Jan-2012
The team
Joëlle Marie, Directeur de Recherche, INSERM
Alain Sureau, Chargé de Recherche, INSERM
Our address
CNRS
Centre de Génétique Moléculaire
Avenue de la Terrasse - Bât. 24
91198 GIF-SUR-YVETTE Cedex
FRANCE
Phone : 33 (0)1 69 82 38 01 - Télécopy : 33 (0)1 69 82 38 77
Interests
Our laboratory focusses on the regulation of alternative splicing and misregulation in myotonic dystrophy type 1 (DM1) .
1) we are using the b-tropomyosin pre-mRNA as a model system to investigate molecular mechanisms that regulate alternative splicing. Our aims are to better understand how splicing regulators modulate splicing choice during myogenic differentiation.
2) DM1 is a neuromuscular disease due to large expansions of CTG-repeats in the 3’ UTR of the DMPK gene. These expansions are transcribed but neither translated and accumulate in the nucleus as discrete RNA foci. One of the most characteristic features of DM pathology is the mis-regulation of splicing of a subset of developmentally regulated transcripts with the reexpression of foetal isoforms in adult tissues. The current model proposes that RNA foci sequester and/or disrupt the function of factors involved in RNA splicing, leading to misregulated splicing events. Our project is to better understand the molecular mechanism leading to myotonic dystrophy (DM). Our goal is to characterize the repertoire of proteins that are sequesterd by the repeats and to identify their function in DM1 pathogenesis.
Sélected publications
Laurent, FX., Sureau, A., Klein AF., Trouslard, F., Gasnier, E., Furling, D., Marie, J. (2011) New function for the RNA helicase p68/DDX5 as a modifier of MBNL1 activity on expanded CUG repeats. Nucleic Acids Res, Epub ahead of print.
Sureau, A., Saulière, J., Expert-Bezançon, A., Marie, J. (2010) CELF and PTB proteins modulate the inclusion of the Β- tropomyosin exon 6B during myogenic differentiation. Exp Cell Res, 317 (1) 94-106.
Laligné, C., Klotz, C., Garreau de Loubresse, N., Lemullois, M., Hori, M., Laurent, F.-X., Papon, J.-F., Louis, B., Cohen, J. and Koll, F. (2010) Bug22p, a conserved centrosomal/ciliary protein also present in higher plants is required for an effective ciliary stroke in Paramecium. Eukaryot Cell, 9 (4) 645-55.
Sauliere, J., Sureau, A., Expert-Bezancon, A. and Marie, J. (2006) The polypyrimidine tract binding protein (PTB) represses splicing of exon 6B from the beta-tropomyosin pre-mRNA by directly interfering with the binding of the U2AF65 subunit. Mol Cell Biol, 26 (23) 8755-69.
Expert-Bezançon, A., Sureau, A., Durosay, P., Salesse, R., Groeneveld, H., Lecaer, J., and Marie, J. (2004). HnRNP A1 and SR proteins, ASF/SF2 and SC35 have antagonistic functions in splicing of beta -tropomyosin exon 6B. J Biol Chem 279, 38249-38259
Expert-Bezançon A, Le Caer J.P and Marie J (2002) HnRNP K is a component of an intronic splicing enhancer complex that activates the splicing of the alternative exon 6A from chicken ?- tropomyosin pre-mRNA. J Biol Chem 277, 16614-16623.
Sureau, A., Gattoni, Y., Dooghen J., Stévenin, J. & Soret, J. (2001). SC35 autoregulates its experession by promoting splicing events that destabilize its mRNAs. EMBO, J. 20 : 1785-1796
Lerga, A. Hallier, M., Delva, L., Orvain, C., Gallais, I., Marie, J., Moreau-Gachelin, F. (2000): Identification of an RNA binding specificity for the potential splicing factors TLS. J Biol Chem.;276 : 6807-6816.
Soret, J., Gattoni, R., Guyon, C., Sureau, A., Popielarz, M., Le Rouzic, E., Dumon, S., Apiou, F., Dutrillaux B., Voss, H., Ansorge, W., Stevenin, J. and Perbal, B. (1998). Characterization of SRp46, a novel human SR splicing factor encoded by a PR264/SC35 retropseudogene. Mol. Cell. Biol., 18: 4924-4934.
Gallego, M.E., Gattoni, R., Stevenin, J., Marie, J. and Expert-Bezançon, A (1997). The SR splicing factors ASF/SF2 and SC35 have antagonistic effects on the intronic enhancer dependant splicing of the ?-tropomyosin alternative exon 6A. EMBO J. 16, 1772-1784.
Sureau, A., Soret, J., Guyon, C., Gaillard, C., Dumon,N S., Keller, M., Crisanti, P. and Perbal, B. (1997) Characterization of multiple alternative RNAs resulting from antisense transcription of the PR264/SC35 splicing factor gene.. Nucleic Acids Res., 25: 4513-4522.
Collaborations
• Nicolas Charlet : Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS UMR 7104, INSERM U596, 67404 Illkirch.
• Christiane Branlant : UMR,CNRS,UHP7214,AREMS, Faculté des Sciences et techniques, Université Henri Poincaré, Bld des Aiguillettes 54506 Vandoeuvre-lès-Nancy
• Geneviève Gourdon : Inserm U781, Clinique Maurice Lamy, Hopital Necker-EM1, 49 rue de Sèvres75015 Paris, France
• Nicolas Sergeant : INSERM Centre Jean-Pierre Aubert, IMPRT, Université Lille II, Place Verdun, 59045 Lille cedex
• Denis Furling : UMRS 974 - Institut de Myologie CNRS UMR7215, Inserm U974, Université Paris6, 105 bld de l'Hôpital, 75013 Paris
