Splicing in Cancer

1 2 3 4 5

Determining the contribution of alternative splicing to cancer biology

Alternative splicing (AS) is a post-transcriptional process whereby the introns and exons of a single gene transcript are differentially spliced to yield multiple mature mRNAs. In eukaryotes, AS plays a central role in both protein diversity and post-transcriptional gene regulation. AS within mRNA coding regions can lead to multiple, functionally diverse protein isoforms from a single gene transcript. AS can also act to introduce or remove regulatory elements to affect the translation, localization or degradation properties of an mRNA.

The majority of human genes are thought to undergo alternative splicing. The capacity of alternative splicing to change the protein function and cellular phenotype made it a prime suspect for human disease. Indeed, it is now linked to many well-known diseases like cystic fibrosis, thalassemia and spinal muscular atrophy.

We have developed tools for discovering and studying the function of cancer associated splice variants. Using these newly developed bioinformatics / genomics techniques we identified two different groups of splicing events required for cell survival, cell cycle progression and apoptosis.

Currently, the work in the laboratory aims at linking splicing factors with cancer specific splicing program and identifies the specific functions of splice variants in the tumor microenvironment and the cell cycle.



Michelle L, Cloutier A, Toutant J, Shkreta L, Thibault P, Durand M, Garneau D, Gendron D, Lapointe E, Couture S, Le Hir H, Klinck R, Elela SA, Prinos P, Chabot B. Proteins associated with the exon junction complex also control the alternative splicing of apoptotic regulators. Mol Cell Biol. 2012 Mar;32(5):954-67.

Venables JP, Klinck R, Koh C, Gervais-Bird J, Bramard A, Inkel L, Durand M, Couture S, Froehlich U, Lapointe E, Lucier JF, Thibault P, Rancourt C, Tremblay K, Prinos P, Chabot B, Elela SA. Cancer-associated regulation of alternative splicing. Nat Struct Mol Biol. 2009 Jun;16(6):670-6.

Venables JP, Brosseau JP, Gadea G, Klinck R, Prinos P, Beaulieu JF, Lapointe E, Durand M, Thibault P, Tremblay K, Rousset F, Tazi J, Abou Elela S, Chabot B. RBFOX2 is an important regulator of mesenchymal tissue-specific splicing in both normal and cancer tissues. Mol Cell Biol. 2013 Jan;33(2):396-405.

Prinos P, Garneau D, Lucier JF, Gendron D, Couture S, Boivin M, Brosseau JP, Lapointe E, Thibault P, Durand M, Tremblay K, Gervais-Bird J, Nwilati H, Klinck R, Chabot B, Perreault JP, Wellinger RJ, Elela SA. Alternative splicing of SYK regulates mitosis and cell survival. Nat Struct Mol Biol. 2011 Jun;18(6):673-9.

Brosseau JP, Lucier JF, Lapointe E, Durand M, Gendron D, Gervais-Bird J, Tremblay K, Perreault JP, Elela SA. High-throughput quantification of splicing isoforms. RNA. 2010 Feb;16(2):442-9.