Gene expression is a multi-step process including transcription, splicing, mRNA export, and translation. Post-transcriptional steps can affect the biological consequences resulting from the transcriptional activity of a gene. In particular, alternative splicing of primary transcripts can lead to the synthesis of protein isoforms having different biological activities or functions. Increasing evidence suggests that all the gene expression steps are mechanically and functionally coordinated. We showed that transcriptional stimuli like steroid hormones simultaneously control transcription and splicing decisions by recruiting coregulators involved in both transcription and splicing processes.
Our goal is to better understand this co-ordinated process and to determine how transcriptional stimuli allow to build up complexes able to control the synthesis, the maturation, and the fate of the products of the target genes they stimulate. We believe that such studies will have an impact on cancer therapies. Indeed, alternative splicing could be a way for cancer cells to increase their protein repertoire and to be able to adapt in their environment or to treatments. A better understanding of how cancer cells use alternative splicing to evolve will allow new therapeutic strategies to block tumour progression. In this respect, our goal is to develop strategies targeting alternative splicing regulation in order to force tumour cells to produce spliced variants having anti-tumour properties.
- Sanchez, G., Bittencourt, D., Laud, K., Barbier, J., Delattre, O., Auboeuf, D., Dutertre, M. (2008). Alteration of cyclin D1 transcript elongation by a mutated transcription factor up-regulates the oncogenic D1b splice isoform in cancer. Proceedings of the National Academy of Sciences USA 2008 Apr 14. [epub ahead of print]
- Barbier, J., Dutertre, M., Bittencourt, D., Sanchez, G., Gratadou, L., de la Grange, P., Auboeuf, D. (2007). Regulation of H-ras Splice Variant Expression by a Cross-talk between the p53 and Nonsense-Mediated mRNA Decay Pathways. Molecular and Cellular Biology (doi:10.1128/MCB.00272-07).
- de la Grange, P., Dutertre, M., Correa, M., Auboeuf, D. (2007). A new advance in alternative splicing databases: from catalogue to detailed analysis of regulation of expression and function of human alternative splicing variants. BMC Bioinformatics 8, 180.
- Auboeuf, D., Batsche, E., Dutertre, M., Muchardt, C., O'Malley, B.W. (2007). Coregulators: transducing signal from transcription to alternative splicing. Trends in Endocrinology and Metabolism 18(3), 122-9. Epub 2007 Feb 21. Review.
- Thill, G., Castelli, V., Pallud, S., Salanoubat, M., Wincker, P., de la Grange, P., Auboeuf, D., Schachter, V., Weissenbach, J. (2006). ASEtrap: a biological method for speeding up the exploration of spliceomes. Genome Research 16(6), 776-86.
- De la Grange, P., Dutertre, M., Martin, N., Auboeuf, D. (2005). FAST DB: A bioinformatics suite for the study of the expression regulation of human gene products . Nucleic Acids Research 28;33(13), 4276-84.
Key lab techniques: in vivo minigene analysis, transcription factors and coregulators analysis; hormone-dependant cancers cell lines (breast, prostate), ChIP,RNA-chIP; bioinformatics; Affymetrix Exon Arrays.
Key lab reagents: dependant cancers cell lines, expression of vectors of nuclear receptor and transcriptional coregulators, hormone-dependant reporter genes.
Lab contact: Didier Auboeuf: email@example.com 
Lab website: http://www.fast-db.com 
RiboSys website: http://www.ribosys.org