The global Protein-RNA interaction map of ESRP1 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,
Kristen W. Lynch,
Russ P. Carstens
Affiliations
Natoya J. Peart
Departments of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding author
Jae Yeon Hwang
Department of Computer Science and Engineering, University of Louisville, Louisville, KY, USA
Mathieu Quesnel-Vallières
Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Matthew J. Sears
Departments of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Yuequin Yang
Departments of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Peter Stoilov
Department of Biochemistry and Cancer Institute, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506, USA
Yoseph Barash
Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Juw Won Park
Department of Computer Science and Engineering, University of Louisville, Louisville, KY, USA; KY INBRE Bioinformatics Core, University of Louisville, Louisville, KY, USA
Kristen W. Lynch
Department of Computer Science and Engineering, University of Louisville, Louisville, KY, USA; Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Russ P. Carstens
Departments of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding author
Summary: The epithelial splicing regulatory proteins, ESRP1 and ESRP2, are essential for mammalian development through the regulation of a global program of alternative splicing of genes involved in the 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 promote either 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.
