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


ABSTRACT: 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.

SUBMITTER: Peart NJ 

PROVIDER: S-EPMC9550651 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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

Peart Natoya J NJ   Hwang Jae Yeon JY   Quesnel-Vallières Mathieu M   Sears Matthew J MJ   Yang Yuequin Y   Stoilov Peter P   Barash Yoseph Y   Park Juw Won JW   Lynch Kristen W KW   Carstens Russ P RP  

iScience 20220923 10


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 integ  ...[more]

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