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The Global Protein-RNA Interaction map of Epithelial Splicing Regulatory Protein 1 defines a post-transcriptional program that is essential for epithelial cell function

Natoya J. Peart, Jae Yeon Hwang, Mathieu Quesnel- Vallières, Matthew J. Sears, Yuequin Yang, Peter Stoilov, Yoseph Barash, Juw Won Park, View ORCID ProfileRuss P. Carstens
doi: https://doi.org/10.1101/2021.05.18.444719
Natoya J. Peart
1Departments of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
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Jae Yeon Hwang
2Department of Computer Science and Engineering, University of Louisville, Louisville, Kentucky, United States of America
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Mathieu Quesnel- Vallières
3Departments of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
4Departments of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
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Matthew J. Sears
1Departments of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
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Yuequin Yang
3Departments of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
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Peter Stoilov
5Department of Biochemistry and Cancer Institute, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV, 26506, USA
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Yoseph Barash
3Departments of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
4Departments of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
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Juw Won Park
2Department of Computer Science and Engineering, University of Louisville, Louisville, Kentucky, United States of America
6Department of KY INBRE Bioinformatics Core, University of Louisville, Louisville, Kentucky, United States of America
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Russ P. Carstens
1Departments of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
3Departments of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
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  • ORCID record for Russ P. Carstens
  • For correspondence: russcars@upenn.edu
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Summary

The epithelial splicing regulatory proteins, ESRP1 and ESRP2 are essential for mammalian development through regulation of a global program of alternative splicing of genes involved in maintenance of epithelial cell function. To further inform our understanding of the molecular functions of ESRP1 we performed enhanced crosslinking immunoprecipitation coupled with high throughput sequencing (eCLIP) in epithelial cells of mouse epidermis. The genome-wide binding sites of ESRP1 were integrated with RNA-Seq analysis of alterations in splicing and total gene expression that result from epidermal ablation of Esrp1 and Esrp2. These studies demonstrated that ESRP1 functions in splicing regulation occur primarily through direct binding in a position-dependent manner to either promote exon inclusion or skipping. In addition, we also identified widespread binding of ESRP1 in 3’ and 5’ untranslated regions (UTRs) of genes involved in epithelial cell function suggesting that its post-transcriptional functions extend beyond splicing regulation.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 18, 2021.
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The Global Protein-RNA Interaction map of Epithelial Splicing Regulatory Protein 1 defines a post-transcriptional program that is essential for epithelial cell function
Natoya J. Peart, Jae Yeon Hwang, Mathieu Quesnel- Vallières, Matthew J. Sears, Yuequin Yang, Peter Stoilov, Yoseph Barash, Juw Won Park, Russ P. Carstens
bioRxiv 2021.05.18.444719; doi: https://doi.org/10.1101/2021.05.18.444719
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The Global Protein-RNA Interaction map of Epithelial Splicing Regulatory Protein 1 defines a post-transcriptional program that is essential for epithelial cell function
Natoya J. Peart, Jae Yeon Hwang, Mathieu Quesnel- Vallières, Matthew J. Sears, Yuequin Yang, Peter Stoilov, Yoseph Barash, Juw Won Park, Russ P. Carstens
bioRxiv 2021.05.18.444719; doi: https://doi.org/10.1101/2021.05.18.444719

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