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.
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BRM knockdown decreases RNA Pol II accumulation on alternatively spliced exons as measured by RNA Pol II ChIP.
“Indeed, BRM knockdown has been shown to decrease RNA Pol II accumulation on alternatively spliced exons as measured by RNA Pol II ChIP (Batsché et al, 2006).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Batsché et al, 2006
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- Authors
- Batsché, E., Yaniv, M., & Muchardt, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Muchardt, Christian
- ORCID
- Muchardt, Christian
- Venue
- Nature Structural & Molecular Biology
- Published
- 2005-12-11
- Volume
- 13
- Issue
- 1
- Pages
- 22-29
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2167212154
- Cited by
- 471
- References
- 50
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 9 · 2023: 11 · 2022: 11 · 2021: 19 · 2020: 19 · 2019: 17 · 2018: 15 · 2017: 12 · 2016: 21 · 2015: 30 · 2014: 23 · 2013: 36 · 2012: 27
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- SWI/SNF complex, BRM, alternative splicing, chromatin remodeling, spliceosome, Sam68, RNA polymerase II, C-terminal domain phosphorylation, CD44, E-cadherin, building information modeling, cyclin D1
- MeSH terms
- DNA-Binding Proteins, Exons, Humans, Phosphoproteins, Phosphorylation, Protein Binding, RNA Polymerase II, RNA, Small Nuclear, Transcription Factors, RNA-Binding Proteins, Alternative Splicing, Hyaluronan Receptors, Protein Subunits, Cell Line, Tumor, Adaptor Proteins, Signal Transducing
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