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James Stévenin

Research Focus

We focus on the molecular mechanisms which regulate alternative splicing in humans. We are particularly interested in the functions of SR (serine/arginine-rich) proteins and hnRNP proteins (hnRNP A/B, hnRNP H, hRBMY). Over the years, we contributed to understand how alternative splicing is regulated, at the molecular level, in a large number of models, such as the adenovirus E1A and HIV-1 pre-mRNAs, CD44, as well as the SR protein encoding SC35 and 9G8 pre-mRNAs.

We have identified and characterised a variety of regulatory RNA elements, as well as the trans-acting proteins that interact with those cis-elements to activate or repress the alternative splicing reactions. We have characterised in details the RNA-binding specificity of the SR proteins 9G8, SRp20 and SC35 and analysed how this is correlated with their properties of splicing activators. We are also studying the potential involvement of a germline-specific hnRNP protein, hRBMY, in the control of alternative splicing during spermatogenesis.

Publications

  1. Dreumont, N., Bourgeois, C.F., Lejeune, F., Liu, Y., Ehrmann, I.E., Elliott, D.J., Stévenin, J. (2010) Human RBMY regulates germline-specific splicing events by modulating the function of the serine/arginine-rich proteins 9G8 and Tra2-{beta}. Journal of Cell Science 123, 40-50.
  2. Dreumont, N., Hardy, S., Behm-Ansmant, I., Kister, L., Branlant, C., Stévenin, J., Bourgeois, C.F. (2009) Antagonistic factors control the unproductive splicing of SC35 terminal intron. Nucleic Acids Research 2009 Dec 3. [Epub ahead of print]
  3. Rajan, P., Dalgliesh, C., Bourgeois, C.F., Heiner, M., Emami, K., Clark, E.L., Bindereif, A., Stévenin, J., Robson, C.N., Leung, H.Y., Elliott, D.J. (2009) Proteomic identification of heterogeneous nuclear ribonucleoprotein L as a novel component of SLM/Sam68 Nuclear Bodies. BMC Cell Biology 10, 82.
  4. Liu, Y., Bourgeois, C.F., Pang, S., Kudla, M., Dreumont, N., Kister, L., Sun, Y.H., Stévenin, J., Elliott, D.J. (2009) The germ cell nuclear proteins hnRNP G-T and RBMY activate a testis-specific exon. PLoS Genetics 2009 Nov 5(11):e1000707.
  5. Saliou, J.M., Bourgeois, C.F., Mena, L.A., Ropers, D., Jacquenet, S., Marchand, V., Stévenin, J., Branlant, C. (2009) Role of RNA structure and protein factors in the control of HIV-1 splicing. Frontiers in Bioscience 14, 2714-29.
  6. Skrisovska L., Bourgeois C.F., Stefl R., Grellscheid S.-N., Kister L., Wenter P., Elliott D.J., Stévenin J. and Allain F.H. (2007). The testis-specific human protein RBMY recognizes RNA through a novel mode of interaction. EMBO Reports 8, 372-379.
  7. Disset A., Bourgeois C.F., Benmalek N., Claustres M., Stévenin J. and Tuffery-Giraud S. (2006). An exon skipping-associated nonsense mutation in the dystrophin gene uncovers a complex interplay between multiple antagonistic splicing elements. Human Molecular Genetics 15, 999-1013.
  8. Venables, J.P., Bourgeois, C.F., Dalgliesh, C., Kister, L., Stévenin, J. and Elliott, D.J. (2005) Upregulation of the ubiquitous alternative splicing factor Tra2ß causes inclusion of a germ cell specific exon. Human Molecular Genetics 14, 2289-2303.
  9. Bourgeois, C.F., Lejeune, F. and Stévenin, J. (2004) Broad specificty of SR (Serine/Arginine) proteins in the regulation of alternative splicing of pre-messenger RNA. Prog. Nucl. Acid Res. Mol. Biol. 78, 37-88.
  10. Ropers, D., Ayadi, L., Gattoni, R., Jacquenet, S., Damier, L., Branlant, C. and Stévenin, J. (2004) Differential effects of the SR proteins 9G8, SC35, ASF/SF2, and SRp40 on the utilization of the A1 to A5 splicing sites of HIV-1 RNA. Journal of Biological Chemistry 279, 29963-73.

Key lab techniques: in vitro splicing assays, protein purification (baculovirus production), production of monoclonal and polyclonal antibodies, immunoprecipitation, SELEX, RNA-protein interactions, RNA chromatography and mass spectrometry, in vivo minigene analysis (transient transfection).

Key lab reagents: expression vectors for SR proteins and various RNA-binding proteins; antisera against various SR proteins, Tra2b and TDP-43; various minigenes for in vitro or in vivo splicing studies.

Lab contact:

Dr Cyril Bourgeois: cyril@igbmc.u-strasbg.fr

Lab website: www-igbmc.u-strasbg.fr/recherche/Dep_GF/Eq_JStev/index_uk.html