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The human SWI/SNF subunit Brm is a regulator of alternative splicing

Nature Structural & Molecular Biology volume 13, pages 22–29 (2006)Cite this article

Abstract

The SWI/SNF (mating-type switch/sucrose nonfermenting) complex involved in chromatin remodeling on promoters has also been detected on the coding region of genes. Here we show that SWI/SNF can function as a regulator of alternative splicing. We found that the catalytic subunit Brm favors inclusion of variant exons in the mRNA of several genes, including E-cadherin, BIM, cyclin D1 and CD44. Consistent with this, Brm associates with several components of the spliceosome and with Sam68, an ERK-activated enhancer of variant exon inclusion. Examination of the CD44 gene revealed that Brm induced accumulation of RNA polymerase II (RNAPII) with a modified CTD phosphorylation pattern on regions encoding variant exons. Altogether, our data suggest that on genes regulated by SWI/SNF, Brm contributes to the crosstalk between transcription and RNA processing by decreasing RNAPII elongation rate and facilitating recruitment of the splicing machinery to variant exons with suboptimal splice sites.

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Figure 1: Brm favors inclusion of alternative exons.
Figure 2: In vivo interaction of Brm with U1 and U5 but not U3 snRNAs.
Figure 3: Brm induces exon inclusion in cooperation with Sam68.
Figure 4: Brm and RNAPII on the coding region of the CD44 gene.
Figure 5: Modified CTD phosphorylation pattern of the RNAPII associated with Brm inside the variant region of the CD44 gene.
Figure 6: Model for the regulation of alternative splicing by Brm on the CD44 gene.

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Acknowledgements

We thank D. Auboeuf, D. Bentley, N. Matter, H. König and B. O'Malley for the gift of plasmids and J. Seeler and J. Weitzman for critical reading of the manuscript. E.B. received a fellowship from the Ligue Nationale Contre le Cancer. The experimental work was supported by grants from the Human Frontier Science Program and Association pour la Recherche sur le Cancer.

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  1. Département de Biologie du Développement, Expression Génétique et Maladies, FRE 2850 du CNRS, Institut Pasteur, Paris, France

    Eric Batsché, Moshe Yaniv & Christian Muchardt

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Correspondence to Christian Muchardt.

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Batsché, E., Yaniv, M. & Muchardt, C. The human SWI/SNF subunit Brm is a regulator of alternative splicing. Nat Struct Mol Biol 13, 22–29 (2006). https://doi.org/10.1038/nsmb1030

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