The global Protein-RNA interaction map of ESRP1 defines a post-transcriptional program that is essential for epithelial cell function

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.

Automated summary

Epithelial splicing regulatory proteins ESRP1 and ESRP2 play crucial roles in the regulation of alternative splicing during mammalian development, particularly in genes involved in maintaining epithelial cell function. Through eCLIP and RNA-Seq analyses, it was found that ESRP1 primarily functions in splicing regulation by directly binding to specific sites to promote exon inclusion or skipping. Additionally, ESRP1 also exhibits widespread binding in the untranslated regions of genes related to epithelial cell function, suggesting its involvement in post-transcriptional regulation beyond splicing.