Parent Category: Laboratoires Published: Thursday, 16 February 2012

RNA Metabolism

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 Jamal TAZI

 

 IGMM - UMR 5535

 1919, route de Mende, 34293 Montpellier

 

Phone: + 33 4 34 35 96 85

Mobile: + 33 6 32 72 77 25

Email: jamal.tazi@igmm.cnrs.fr

 

Website

 

 

Research in our laboratory focuses on the role of splicing factors in controlling entire biological pathways that are important for normal as well as pathological developmental processes. Alternative pathways for processing the primary transcript can profoundly affect the diversity and function of the protein products that are generated from a single gene during cell differentiation and development of multicellular organisms. Mis-regulated splicing events are also the cause of an increasing number of human diseases and are therefore intriguing targets for therapeutic intervention. Despite the prevalence and importance of alternative splicing for understanding the information content of genomes, and the widespread implications of the process in human pathologies, our knowledge of the molecular mechanisms that regulate alternative splicing in vivo remains very limited. We are using both Drosophila and mouse models to decipher this mechanism. We have also dedicated much effort to decipher the underlying mechanism of splicing mutations and to the search for chemical molecules able to selectively interfere with the activity of proteins member of the SR family of splicing regulators and putatively apt to correct pathological splicing events. This knowledge will now be applied to characterize and pharmacologically modulate splicing events involved in HIV infection, ageing and metastatic Cancer. Through generation and optimization of small molecules inhibiting alternative splicing mechanisms, our group is developing therapeutic leads, opening the way to new therapeutic solutions. To achieve this goal a collaborative laboratory "Splicos Therapeutics" was created between public institutions CNRS, Universities I and II and a startup company Splicos, in order to perform the discovery works.

 

Keywords: RNA metabolism, Alternative splicing, premature aging, splicing pharmacology, stem cells, drosophila development

 

 

Main publications

  • Revisiting G3BP1 as a RasGAP Binding Protein: Sensitization of Tumor Cells to Chemotherapy by the RasGAP 317–326 Sequence Does Not Involve G3BP1. PLOS One, In Press
  • Osorio,F.G., Navarro,C.L., Cadinanos,J., Lopez-Mejia,I.C., Quiros,P.M., Bartoli,C., Rivera,J., Tazi,J., Guzman,G., Varela,I., et al. (2011) Splicing-directed therapy in a new mouse model of human accelerated aging. Sci. Transl. Med., 3, 106ra107.
  • Venables,J.P., Tazi,J., Juge,F. (2011) Regulated functional alternative splicing in Drosophila. Nucleic Acids Res..
  • Lopez-Mejia,I.C., Vautrot,V., De,T.M., Behm-Ansmant,I., Bourgeois,C.F., Navarro,C.L., Osorio,F.G., Freije,J.M., Stevenin,J., De Sandre-Giovannoli,A., et al. (2011) A conserved splicing mechanism of the LMNA gene controls premature aging. Hum. Mol. Genet., 20, 4540-4555.
  • Venables,J.P., Vignal,E., Baghdiguian,S., Fort,P., Tazi,J. (2011) Tissue-Specific Alternative Splicing of Tak1 Is Conserved in Deuterostomes. Mol. Biol. Evol..
  • Ghigna,C., De,T.M., Bonomi,S., Valacca,C., Gallo,S., Apicella,M., Eperon,I., Tazi,J., Biamonti,G. (2010) Pro-metastatic splicing of Ron proto-oncogene mRNA can be reversed: therapeutic potential of bifunctional oligonucleotides and indole derivatives. RNA. Biol., 7, 495-503.
  • Juge,F., Fernando,C., Fic,W., Tazi,J. (2010) The SR protein B52/SRp55 is required for DNA topoisomerase I recruitment to chromatin, mRNA release and transcription shutdown. PLoS. Genet., 6.
  • Schneider,M., Will,C.L., Anokhina,M., Tazi,J., Urlaub,H., Luhrmann,R. (2010) Exon definition complexes contain the tri-snRNP and can be directly converted into B-like precatalytic splicing complexes. Mol. Cell, 38, 223-235.
  • Dutertre,M., Lacroix-Triki,M., Driouch,K., de la Grange,P., Gratadou,L., Beck,S., Millevoi,S., Tazi,J., Lidereau,R., Vagner,S., Auboeuf,D. (2010) Exon-based clustering of murine breast tumor transcriptomes reveals alternative exons whose expression is associated with metastasis. Cancer Res., 70, 896-905.
  • Tazi,J., Bakkour,N., Marchand,V., Ayadi,L., Aboufirassi,A., Branlant,C. (2010) Alternative splicing: regulation of HIV-1 multiplication as a target for therapeutic action. FEBS J., 277, 867-876.

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