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RBFOX2 Is an Important Regulator of Mesenchymal Tissue-Specific Splicing in both Normal and Cancer Tissues

Lookup NU author(s): Dr Julian Venables


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Alternative splicing provides a critical and flexible layer of regulation intervening in many biological processes to regulate the diversity of proteins and impact cell phenotype. To identify alternative splicing differences that distinguish epithelial from mesenchymal tissues, we have investigated hundreds of cassette exons using a high-throughput reverse transcription-PCR (RT-PCR) platform. Extensive changes in splicing were noted between epithelial and mesenchymal tissues in both human colon and ovarian tissues, with many changes from mostly one splice variant to predominantly the other. Remarkably, many of the splicing differences that distinguish normal mesenchymal from normal epithelial tissues matched those that differentiate normal ovarian tissues from ovarian cancer. Furthermore, because splicing profiling could classify cancer cell lines according to their epithelial/mesenchymal characteristics, we used these cancer cell lines to identify regulators for these specific splicing signatures. By knocking down 78 potential splicing factors in five cell lines, we provide an extensive view of the complex regulatory landscape associated with the epithelial and mesenchymal states, thus revealing that RBFOX2 is an important driver of mesenchymal tissue-specific splicing.

Publication metadata

Author(s): 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

Publication type: Article

Publication status: Published

Journal: Molecular and Cellular Biology

Year: 2013

Volume: 33

Issue: 2

Pages: 396-405

Print publication date: 12/11/2012

ISSN (print): 0270-7306

ISSN (electronic): 1098-5549

Publisher: American Society for Microbiology


DOI: 10.1128/MCB.01174-12

PubMed id: 23149937


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