title: RBFOX2 is an important regulator of mesenchymal tissue-specific splicing in both normal and cancer tissues.
abstract: 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.
authors.affiliation: Laboratoire de génomique fonctionnelle de l'Université de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Venables
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Brosseau
authors.forename: Gilles
authors.initials: G
authors.lastname: Gadea
authors.forename: Roscoe
authors.initials: R
authors.lastname: Klinck
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Prinos
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Beaulieu
authors.forename: Elvy
authors.initials: E
authors.lastname: Lapointe
authors.forename: Mathieu
authors.initials: M
authors.lastname: Durand
authors.forename: Philippe
authors.initials: P
authors.lastname: Thibault
authors.forename: Karine
authors.initials: K
authors.lastname: Tremblay
authors.forename: François
authors.initials: F
authors.lastname: Rousset
authors.forename: Jamal
authors.initials: J
authors.lastname: Tazi
authors.forename: Sherif
authors.initials: S
authors.lastname: Abou Elela
authors.forename: Benoit
authors.initials: B
authors.lastname: Chabot
mesh_terms: D017398:Alternative Splicing; D045744:Cell Line, Tumor; D019295:Computational Biology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005091:Exons; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C493663:MBNL1 protein, human; C454924:RBFOX2 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins