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The SWI/SNF subunit BRG1 affects alternative splicing by changing RNA binding factor interactions with nascent RNA
BRG1 and BRM are ATPase core subunits of the human SWI/SNF chromatin remodelling complexes mainly associated with transcriptional initiation. They also have a role in alternative splicing, which has been shown for BRM-containing SWI/SNF complexes at a few genes. Here, we have identified a subset of...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960663/ https://www.ncbi.nlm.nih.gov/pubmed/35187582 http://dx.doi.org/10.1007/s00438-022-01863-9 |
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author | Gañez-Zapater, Antoni Mackowiak, Sebastian D. Guo, Yuan Tarbier, Marcel Jordán-Pla, Antonio Friedländer, Marc R. Visa, Neus Östlund Farrants, Ann-Kristin |
author_facet | Gañez-Zapater, Antoni Mackowiak, Sebastian D. Guo, Yuan Tarbier, Marcel Jordán-Pla, Antonio Friedländer, Marc R. Visa, Neus Östlund Farrants, Ann-Kristin |
author_sort | Gañez-Zapater, Antoni |
collection | PubMed |
description | BRG1 and BRM are ATPase core subunits of the human SWI/SNF chromatin remodelling complexes mainly associated with transcriptional initiation. They also have a role in alternative splicing, which has been shown for BRM-containing SWI/SNF complexes at a few genes. Here, we have identified a subset of genes which harbour alternative exons that are affected by SWI/SNF ATPases by expressing the ATPases BRG1 and BRM in C33A cells, a BRG1- and BRM-deficient cell line, and analysed the effect on splicing by RNA sequencing. BRG1- and BRM-affected sub-sets of genes favouring both exon inclusion and exon skipping, with only a minor overlap between the ATPase. Some of the changes in alternative splicing induced by BRG1 and BRM expression did not require the ATPase activity. The BRG1-ATPase independent included exons displayed an exon signature of a high GC content. By investigating three genes with exons affected by the BRG-ATPase-deficient variant, we show that these exons accumulated phosphorylated RNA pol II CTD, both serine 2 and serine 5 phosphorylation, without an enrichment of the RNA polymerase II. The ATPases were recruited to the alternative exons, together with both core and signature subunits of SWI/SNF complexes, and promoted the binding of RNA binding factors to chromatin and RNA at the alternative exons. The interaction with the nascent RNP, however, did not reflect the association to chromatin. The hnRNPL, hnRNPU and SAM68 proteins associated with chromatin in cells expressing BRG1 and BRM wild type, but the binding of hnRNPU to the nascent RNP was excluded. This suggests that SWI/SNF can regulate alternative splicing by interacting with splicing-RNA binding factor and influence their binding to the nascent pre-mRNA particle. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00438-022-01863-9. |
format | Online Article Text |
id | pubmed-8960663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-89606632022-04-07 The SWI/SNF subunit BRG1 affects alternative splicing by changing RNA binding factor interactions with nascent RNA Gañez-Zapater, Antoni Mackowiak, Sebastian D. Guo, Yuan Tarbier, Marcel Jordán-Pla, Antonio Friedländer, Marc R. Visa, Neus Östlund Farrants, Ann-Kristin Mol Genet Genomics Original Article BRG1 and BRM are ATPase core subunits of the human SWI/SNF chromatin remodelling complexes mainly associated with transcriptional initiation. They also have a role in alternative splicing, which has been shown for BRM-containing SWI/SNF complexes at a few genes. Here, we have identified a subset of genes which harbour alternative exons that are affected by SWI/SNF ATPases by expressing the ATPases BRG1 and BRM in C33A cells, a BRG1- and BRM-deficient cell line, and analysed the effect on splicing by RNA sequencing. BRG1- and BRM-affected sub-sets of genes favouring both exon inclusion and exon skipping, with only a minor overlap between the ATPase. Some of the changes in alternative splicing induced by BRG1 and BRM expression did not require the ATPase activity. The BRG1-ATPase independent included exons displayed an exon signature of a high GC content. By investigating three genes with exons affected by the BRG-ATPase-deficient variant, we show that these exons accumulated phosphorylated RNA pol II CTD, both serine 2 and serine 5 phosphorylation, without an enrichment of the RNA polymerase II. The ATPases were recruited to the alternative exons, together with both core and signature subunits of SWI/SNF complexes, and promoted the binding of RNA binding factors to chromatin and RNA at the alternative exons. The interaction with the nascent RNP, however, did not reflect the association to chromatin. The hnRNPL, hnRNPU and SAM68 proteins associated with chromatin in cells expressing BRG1 and BRM wild type, but the binding of hnRNPU to the nascent RNP was excluded. This suggests that SWI/SNF can regulate alternative splicing by interacting with splicing-RNA binding factor and influence their binding to the nascent pre-mRNA particle. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00438-022-01863-9. Springer Berlin Heidelberg 2022-02-20 2022 /pmc/articles/PMC8960663/ /pubmed/35187582 http://dx.doi.org/10.1007/s00438-022-01863-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Gañez-Zapater, Antoni Mackowiak, Sebastian D. Guo, Yuan Tarbier, Marcel Jordán-Pla, Antonio Friedländer, Marc R. Visa, Neus Östlund Farrants, Ann-Kristin The SWI/SNF subunit BRG1 affects alternative splicing by changing RNA binding factor interactions with nascent RNA |
title | The SWI/SNF subunit BRG1 affects alternative splicing by changing RNA binding factor interactions with nascent RNA |
title_full | The SWI/SNF subunit BRG1 affects alternative splicing by changing RNA binding factor interactions with nascent RNA |
title_fullStr | The SWI/SNF subunit BRG1 affects alternative splicing by changing RNA binding factor interactions with nascent RNA |
title_full_unstemmed | The SWI/SNF subunit BRG1 affects alternative splicing by changing RNA binding factor interactions with nascent RNA |
title_short | The SWI/SNF subunit BRG1 affects alternative splicing by changing RNA binding factor interactions with nascent RNA |
title_sort | swi/snf subunit brg1 affects alternative splicing by changing rna binding factor interactions with nascent rna |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960663/ https://www.ncbi.nlm.nih.gov/pubmed/35187582 http://dx.doi.org/10.1007/s00438-022-01863-9 |
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