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PMID: 19448617 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cancer-associated regulation of alternative splicing.

Nature structural & molecular biology ·Vol. 16 ·No. 6 ·2009-06-00 ·Pages 670-6

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

Abstract

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.

MeSH Terms
Alternative Splicing Amino Acid Motifs Binding Sites Breast Neoplasms/metabolism Cell Line, Tumor Cell Proliferation Exons Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Neoplasms/genetics,metabolism Ovarian Neoplasms/metabolism RNA-Binding Proteins/chemistry Sequence Analysis, DNA
Chemicals
RNA-Binding Proteins
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Venables Julian P
Laboratoire de génomique fonctionnelle de l'Université de Sherbrooke, Sherbrooke, Québec, Canada.
Klinck Roscoe
Koh ChuShin
Gervais-Bird Julien
Bramard Anne
Inkel Lyna
Durand Mathieu
Couture Sonia
Froehlich Ulrike
Lapointe Elvy
Lucier Jean-François
Thibault Philippe
Rancourt Claudine
Tremblay Karine
Prinos Panagiotis
Chabot Benoit
Elela Sherif Abou
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1608
Published
2009-06-00
Epub
2009-00-17
Pages
670-6
Language
English
Region
United States
NLM ID
101186374
Subset
IM
External Links
PubMed source DOI: 10.1038/nsmb.1608 View journal details
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