An ESRP‐regulated splicing programme is abrogated during the epithelial–mesenchymal transition
Open accessAbstract
Alternative splicing achieves coordinated changes in post-transcriptional gene expression programmes through the activities of diverse RNA-binding proteins. Epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) are cell-type-specific regulators of transcripts that switch splicing during the epithelial-mesenchymal transition (EMT). To define a comprehensive programme of alternative splicing that is regulated during the EMT, we identified an extensive ESRP-regulated splicing network of hundreds of alternative splicing events within numerous genes with functions in cell-cell adhesion, polarity, and migration. Loss of this global ESRP-regulated epithelial splicing programme induces the phenotypic changes in cell morphology that are observed during the EMT. Components of this splicing signature provide novel molecular markers that can be used to characterize the EMT. Bioinformatics and experimental approaches revealed a high-affinity ESRP-binding motif and a predictive RNA map that governs their activity. This work establishes the ESRPs as coordinators of a complex alternative splicing network that adds an important post-transcriptional layer to the changes in gene expression that underlie epithelial-mesenchymal transitions during development and disease.
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ESRPs are a conserved family of epithelial-specific RBPs that exert broad control over many physiological processes, including tissue regeneration and the epithelial-mesenchymal transition (EMT) during development and cancer progression.
“ESRPs are a conserved family of epithelial-specific RBPs that exert broad control over many physiological processes, including tissue regeneration and the epithelial–mesenchymal transition (EMT) during development and cancer progression (Warzecha et al. 2010; Lu et al. 2013; Bebee et al. 2015; Derham and Kalsotra 2023).”
From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Warzecha et al. 2010
The Introduction (page unavailable) identifies ESRP1 and ESRP2 as epithelial-specific splicing regulators and reports their downregulation during EMT; the microarray-results section calls them phylogenetically conserved splicing factors. The paper identifies hundreds of ESRP-regulated events and reports EMT-like changes after ESRP knockdown, but our copy does not establish a role for ESRPs in tissue regeneration or directly demonstrate their control of EMT during development or cancer progression. (LLM, conf=0.87)
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Cites
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“Current markers used to characterize the EMT rely on collections of transcript or protein biomarkers that have utility in different subtypes of EMT (Zeisberg and Neilson, 2009).”
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ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation
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Self-citation
- Authors
- Warzecha, C. C., Jiang, P., Amirikian, K., Dittmar, K. A., Lu, H., Shen, S., Guo, W., Xing, Y., & Carstens, R. P.
- Affiliations
- University of Pennsylvania (US)
- University of Iowa (US)
- Corresponding author
- Carstens, Russ P
- Venue
- The EMBO Journal
- Published
- 2010-08-13
- Volume
- 29
- Issue
- 19
- Pages
- 3286-3300
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2957203
- OpenAlex
- W2133735831
- Cited by
- 383
- References
- 4
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 9 · 2023: 16 · 2022: 21 · 2021: 26 · 2020: 27 · 2019: 26 · 2018: 25 · 2017: 26 · 2016: 37 · 2015: 25 · 2014: 21 · 2013: 40 · 2012: 29
- FWCI
- 11.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Edward Mallinckrodt, Jr. Foundation
- National Institutes of Health (GM085146, GM088809)
- National Human Genome Research Institute (R01HG004634)
- National Cancer Institute (R01CA093769)
- National Institute of General Medical Sciences (R01GM085146, T32GM008216, T32 GM08216, R01GM088809)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- epithelial-mesenchymal transition, alternative splicing, ESRP1, ESRP2, RNA-binding proteins, cell-cell adhesion, cell polarity, cell migration, post-transcriptional regulation
- MeSH terms
- Binding Sites, Cell Adhesion, Cell Differentiation, Cell Line, Cell Movement, Epithelial Cells, Fluorescent Antibody Technique, Gene Expression Regulation, Humans, Mesoderm, Immunoblotting, RNA-Binding Proteins, Cell Polarity, Alternative Splicing, Computational Biology, Reverse Transcriptase Polymerase Chain Reaction, Electrophoretic Mobility Shift Assay, Vesicular Transport Proteins, Microarray Analysis
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