Genome-Wide Determination of a Broad ESRP-Regulated Posttranscriptional Network by High-Throughput Sequencing
Open accessAbstract
Tissue-specific alternative splicing is achieved through the coordinated assembly of RNA binding proteins at specific sites to enhance or silence splicing at nearby splice sites. We used high-throughput sequencing (RNA-Seq) to investigate the complete spectrum of alternative splicing events that are regulated by the epithelium-specific splicing regulatory proteins ESRP1 and ESRP2. We also combined this analysis with direct RNA sequencing (DRS) to reveal ESRP-mediated regulation of alternative polyadenylation. To define binding motifs that mediate direct regulation of splicing and polyadenylation by ESRP, SELEX-Seq analysis was performed, coupling traditional SELEX with high-throughput sequencing. Identification and scoring of high-affinity ESRP1 binding motifs within ESRP target genes allowed the generation of RNA maps that define the position-dependent activity of the ESRPs in regulating cassette exons and alternative 3' ends. These extensive analyses provide a comprehensive picture of the functions of the ESRPs in an epithelial posttranscriptional gene expression program.
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The in vivo ESRP2-binding site determination with FLAG-ESRP2 eCLIP is accurate, as the identified UG-containing motifs match those identified in vitro by SELEX-seq and RNA bind-n-seq.
“Similar UG-containing sequence motifs for ESRP proteins have been identified in vitro by SELEX-seq (Dittmar et al. 2012) and RNA bind-n-seq (Nostrand et al. 2020), confirming the accuracy of our in vivo ESRP2-binding site determination with FLAG-ESRP2 eCLIP.”
From ESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation (2025) · cites this paper as Dittmar et al. 2012
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Self-citationESRP2–microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation
Bangru, S., Chen, J., Baker, N., Das, D., Chembazhi, U. V., Derham, J. M., Chorghade, S., Arif, W., Alencastro, F., Duncan, A. W., et al. (2025) · Genes & Development · doi:10.1101/gad.352129.124 · Cited by 4 · see citing works
Self-citation
- Authors
- Dittmar, K. A., Jiang, P., Park, J. W., Amirikian, K., Wan, J., Shen, S., Xing, Y., & Carstens, R. P.
- Affiliations
- University of Pennsylvania (US)
- University of Iowa (US)
- Renal Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2012-04-01
- Volume
- 32
- Issue
- 8
- Pages
- 1468-1482
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC3318588
- OpenAlex
- W2136041152
- Cited by
- 139
- References
- 4
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 13 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 10 · 2019: 11 · 2018: 10 · 2017: 11 · 2016: 17 · 2015: 5 · 2014: 19 · 2013: 14 · 2012: 8
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institute of Clinical and Translational Sciences
- Edward Mallinckrodt, Jr. Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL007638)
- National Institute of General Medical Sciences (R01GM088342, R01GM088809)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK054759)
- National Center for Research Resources (UL1RR024979)
- 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
- ESRP1, ESRP2, alternative splicing, alternative polyadenylation, RNA-binding proteins, post-transcriptional regulation, direct RNA sequencing, cassette exons, tissue-specific gene expression, epithelial cells
- MeSH terms
- Base Sequence, Binding Sites, Epithelium, Humans, Organ Specificity, Genome, Human, RNA-Binding Proteins, Alternative Splicing, Sequence Analysis, RNA, RNA Splice Sites, Genome-Wide Association Study, Nucleotide Motifs
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