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Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT
The epithelial–mesenchymal transition (EMT) is a fundamental developmental process that is abnormally activated in cancer metastasis. Dynamic changes in alternative splicing occur during EMT. ESRP1 and hnRNPM are splicing regulators that promote an epithelial splicing program and a mesenchymal splic...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140460/ https://www.ncbi.nlm.nih.gov/pubmed/30042172 http://dx.doi.org/10.1261/rna.066712.118 |
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author | Harvey, Samuel E. Xu, Yilin Lin, Xiaodan Gao, Xin D. Qiu, Yushan Ahn, Jaegyoon Xiao, Xinshu Cheng, Chonghui |
author_facet | Harvey, Samuel E. Xu, Yilin Lin, Xiaodan Gao, Xin D. Qiu, Yushan Ahn, Jaegyoon Xiao, Xinshu Cheng, Chonghui |
author_sort | Harvey, Samuel E. |
collection | PubMed |
description | The epithelial–mesenchymal transition (EMT) is a fundamental developmental process that is abnormally activated in cancer metastasis. Dynamic changes in alternative splicing occur during EMT. ESRP1 and hnRNPM are splicing regulators that promote an epithelial splicing program and a mesenchymal splicing program, respectively. The functional relationships between these splicing factors in the genome scale remain elusive. Comparing alternative splicing targets of hnRNPM and ESRP1 revealed that they coregulate a set of cassette exon events, with the majority showing discordant splicing regulation. Discordant splicing events regulated by hnRNPM show a positive correlation with splicing during EMT; however, concordant events do not, indicating the role of hnRNPM in regulating alternative splicing during EMT is more complex than previously understood. Motif enrichment analysis near hnRNPM–ESRP1 coregulated exons identifies guanine–uridine rich motifs downstream from hnRNPM-repressed and ESRP1-enhanced exons, supporting a general model of competitive binding to these cis-elements to antagonize alternative splicing. The set of coregulated exons are enriched in genes associated with cell migration and cytoskeletal reorganization, which are pathways associated with EMT. Splicing levels of coregulated exons are associated with breast cancer patient survival and correlate with gene sets involved in EMT and breast cancer subtyping. This study identifies complex modes of interaction between hnRNPM and ESRP1 in regulation of splicing in disease-relevant contexts. |
format | Online Article Text |
id | pubmed-6140460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61404602019-10-01 Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT Harvey, Samuel E. Xu, Yilin Lin, Xiaodan Gao, Xin D. Qiu, Yushan Ahn, Jaegyoon Xiao, Xinshu Cheng, Chonghui RNA Report The epithelial–mesenchymal transition (EMT) is a fundamental developmental process that is abnormally activated in cancer metastasis. Dynamic changes in alternative splicing occur during EMT. ESRP1 and hnRNPM are splicing regulators that promote an epithelial splicing program and a mesenchymal splicing program, respectively. The functional relationships between these splicing factors in the genome scale remain elusive. Comparing alternative splicing targets of hnRNPM and ESRP1 revealed that they coregulate a set of cassette exon events, with the majority showing discordant splicing regulation. Discordant splicing events regulated by hnRNPM show a positive correlation with splicing during EMT; however, concordant events do not, indicating the role of hnRNPM in regulating alternative splicing during EMT is more complex than previously understood. Motif enrichment analysis near hnRNPM–ESRP1 coregulated exons identifies guanine–uridine rich motifs downstream from hnRNPM-repressed and ESRP1-enhanced exons, supporting a general model of competitive binding to these cis-elements to antagonize alternative splicing. The set of coregulated exons are enriched in genes associated with cell migration and cytoskeletal reorganization, which are pathways associated with EMT. Splicing levels of coregulated exons are associated with breast cancer patient survival and correlate with gene sets involved in EMT and breast cancer subtyping. This study identifies complex modes of interaction between hnRNPM and ESRP1 in regulation of splicing in disease-relevant contexts. Cold Spring Harbor Laboratory Press 2018-10 /pmc/articles/PMC6140460/ /pubmed/30042172 http://dx.doi.org/10.1261/rna.066712.118 Text en © 2018 Harvey et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Report Harvey, Samuel E. Xu, Yilin Lin, Xiaodan Gao, Xin D. Qiu, Yushan Ahn, Jaegyoon Xiao, Xinshu Cheng, Chonghui Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT |
title | Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT |
title_full | Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT |
title_fullStr | Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT |
title_full_unstemmed | Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT |
title_short | Coregulation of alternative splicing by hnRNPM and ESRP1 during EMT |
title_sort | coregulation of alternative splicing by hnrnpm and esrp1 during emt |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140460/ https://www.ncbi.nlm.nih.gov/pubmed/30042172 http://dx.doi.org/10.1261/rna.066712.118 |
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