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Cancer-associated regulation of alternative splicing

Lookup NU author(s): Dr Julian Venables


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Alternative splicing of pre-mRNA increases the diversity of protein functions. Here we show that about half of all active alternative splicing events in ovarian and breast tissues are changed in tumors, and many seem to be regulated by a single factor; sequence analysis revealed binding sites for the RNA binding protein FOX2 downstream of one-third of the exons skipped in cancer. High-resolution analysis of FOX2 binding sites defined the precise positions relative to alternative exons at which the protein may function as either a silencer or an enhancer. Most of the identified targets were shifted in the same direction by FOX2 depletion in cell lines as they were in breast and ovarian cancer tissues. Notably, we found expression of FOX2 itself is downregulated in ovarian cancer and its splicing is altered in breast cancer samples. These results suggest that the decreased expression of FOX2 in cancer tissues modulates splicing and controls proliferation.

Publication metadata

Author(s): 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

Publication type: Article

Publication status: Published

Journal: Nature Structural and Molecular Biology

Year: 2009

Volume: 16

Issue: 6

Pages: 670-676

ISSN (print): 1545-9993

ISSN (electronic): 1545-9985

Publisher: Nature Publishing Group


DOI: 10.1038/nsmb.1608


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