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RBFOX2 alters splicing outcome in distinct binding modes with multiple protein partners
RBFOX2 controls the splicing of a large number of transcripts implicated in cell differentiation and development. Parsing RNA-binding protein datasets, we uncover that RBFOX2 can interact with hnRNPC, hnRNPM and SRSF1 to regulate splicing of a broad range of splicing events using different sequence...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373071/ https://www.ncbi.nlm.nih.gov/pubmed/34244793 http://dx.doi.org/10.1093/nar/gkab595 |
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author | Zhou, Delong Couture, Sonia Scott, Michelle S Abou Elela, Sherif |
author_facet | Zhou, Delong Couture, Sonia Scott, Michelle S Abou Elela, Sherif |
author_sort | Zhou, Delong |
collection | PubMed |
description | RBFOX2 controls the splicing of a large number of transcripts implicated in cell differentiation and development. Parsing RNA-binding protein datasets, we uncover that RBFOX2 can interact with hnRNPC, hnRNPM and SRSF1 to regulate splicing of a broad range of splicing events using different sequence motifs and binding modes. Using immunoprecipitation, specific RBP knockdown, RNA-seq and splice-sensitive PCR, we show that RBFOX2 can target splice sites using three binding configurations: single, multiple or secondary modes. In the single binding mode RBFOX2 is recruited to its target splice sites through a single canonical binding motif, while in the multiple binding mode RBFOX2 binding sites include the adjacent binding of at least one other RNA binding protein partner. Finally, in the secondary binding mode RBFOX2 likely does not bind the RNA directly but is recruited to splice sites lacking its canonical binding motif through the binding of one of its protein partners. These dynamic modes bind distinct sets of transcripts at different positions and distances relative to alternative splice sites explaining the heterogeneity of RBFOX2 targets and splicing outcomes. |
format | Online Article Text |
id | pubmed-8373071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-83730712021-08-19 RBFOX2 alters splicing outcome in distinct binding modes with multiple protein partners Zhou, Delong Couture, Sonia Scott, Michelle S Abou Elela, Sherif Nucleic Acids Res RNA and RNA-protein complexes RBFOX2 controls the splicing of a large number of transcripts implicated in cell differentiation and development. Parsing RNA-binding protein datasets, we uncover that RBFOX2 can interact with hnRNPC, hnRNPM and SRSF1 to regulate splicing of a broad range of splicing events using different sequence motifs and binding modes. Using immunoprecipitation, specific RBP knockdown, RNA-seq and splice-sensitive PCR, we show that RBFOX2 can target splice sites using three binding configurations: single, multiple or secondary modes. In the single binding mode RBFOX2 is recruited to its target splice sites through a single canonical binding motif, while in the multiple binding mode RBFOX2 binding sites include the adjacent binding of at least one other RNA binding protein partner. Finally, in the secondary binding mode RBFOX2 likely does not bind the RNA directly but is recruited to splice sites lacking its canonical binding motif through the binding of one of its protein partners. These dynamic modes bind distinct sets of transcripts at different positions and distances relative to alternative splice sites explaining the heterogeneity of RBFOX2 targets and splicing outcomes. Oxford University Press 2021-07-09 /pmc/articles/PMC8373071/ /pubmed/34244793 http://dx.doi.org/10.1093/nar/gkab595 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | RNA and RNA-protein complexes Zhou, Delong Couture, Sonia Scott, Michelle S Abou Elela, Sherif RBFOX2 alters splicing outcome in distinct binding modes with multiple protein partners |
title | RBFOX2 alters splicing outcome in distinct binding modes with multiple protein partners |
title_full | RBFOX2 alters splicing outcome in distinct binding modes with multiple protein partners |
title_fullStr | RBFOX2 alters splicing outcome in distinct binding modes with multiple protein partners |
title_full_unstemmed | RBFOX2 alters splicing outcome in distinct binding modes with multiple protein partners |
title_short | RBFOX2 alters splicing outcome in distinct binding modes with multiple protein partners |
title_sort | rbfox2 alters splicing outcome in distinct binding modes with multiple protein partners |
topic | RNA and RNA-protein complexes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373071/ https://www.ncbi.nlm.nih.gov/pubmed/34244793 http://dx.doi.org/10.1093/nar/gkab595 |
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