Open AccessAlternative splicing regulates distinct subcellular localization of Epithelial splicing regulatory protein 1 (Esrp1) isoforms
Author(s) -
Youshan Yang,
Russ P. Carstens
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-03180-3
Subject(s) - alternative splicing , gene isoform , subcellular localization , rna splicing , protein subcellular localization prediction , microbiology and biotechnology , biology , computational biology , gene , genetics , rna
Epithelial-Splicing-Regulatory-Protein 1 (Esrp1) is a cell-type specific RNA-binding protein (RBP) that is essential for mammalian development through maintenance of epithelial cell properties including barrier function. Esrp1 also regulates splicing during the epithelial to mesenchymal transition (EMT). It contains three highly conserved RNA recognition motifs (RRMs) in the absence of other clearly defined protein domains. Esrp1 itself is also alternatively spliced to produce multiple protein isoforms. Here we determined that two competing alternative 5′ splice sites in exon 12 yield Esrp1 isoforms with differential nucleocytoplasmic localization. We carried out a detailed characterization of the Esrp1 peptide that is sufficient to confer nuclear localization. Furthermore, we identified splice variants encoding distinct nuclear and cytoplasmic isoforms of fusilli, the D . Melanogaster Esrp1 ortholog. Our observations demonstrate that the production of both nuclear and cytoplasmic Esrp1 isoforms through alternative splicing is phylogenetically conserved; strongly suggesting it is biologically significant. Thus, while previous studies have described extensive regulation by nuclear Esrp1 to promote epithelial specific splicing, it will be of great interest to study the contribution of cytoplasmic Esrp1 in maintenance of epithelial cell functions.