title: The human SWI/SNF subunit Brm is a regulator of alternative splicing.
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.
authors.affiliation: Expression Génétique et Maladies, FRE 2850 du CNRS, Département de Biologie du Développement, Institut Pasteur, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Batsché
authors.forename: Moshe
authors.initials: M
authors.lastname: Yaniv
authors.forename: Christian
authors.initials: C
authors.lastname: Muchardt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; C489559:KHDRBS1 protein, human; D010750:Phosphoproteins; D021122:Protein Subunits; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; C084011:SMARCA2 protein, human; D014157:Transcription Factors; D012319:RNA Polymerase II