Alternative splicing regulates distinct subcellular localization of Epithelial splicing regulatory protein 1 (Esrp1) isoforms.
Alternative splicing regulates distinct subcellular localization of Epithelial splicing regulatory protein 1 (Esrp1) isoforms.
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DOI：
10.1038/s41598-017-03180-3
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发表时间：
2017-06-20
影响因子：
4.6
通讯作者：
Carstens RP
中科院分区：
文献类型：
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作者：
Yang Y;Carstens RP
上皮剪接调节蛋白1（Epithelial-Splicing-Regulatory-Protein 1，Esrp 1）是一种细胞类型特异性的RNA结合蛋白（RNA binding protein，RBP），通过维持上皮细胞的特性（包括屏障功能）对哺乳动物的发育至关重要。Esrp 1还调节上皮向间充质转化（EMT）过程中的剪接。它包含三个高度保守的RNA识别基序（RRM），在没有其他明确定义的蛋白质结构域。Esrp 1本身也被选择性剪接以产生多种蛋白质同种型。在这里，我们确定了外显子12中的两个竞争性选择性5′剪接位点产生具有差异核质定位的Esrp 1亚型。我们进行了详细的表征的Esrp 1肽，足以赋予核定位。此外，我们还鉴定了编码不同核和细胞质梭菌亚型的剪接变体，D。黑腹菌Esrp 1直系同源物我们的观察结果表明，通过选择性剪接的细胞核和细胞质Esrp 1亚型的生产是非遗传保守的，强烈表明它是生物学意义。因此，虽然以前的研究已经描述了广泛的调节核Esrp 1，以促进上皮特异性剪接，这将是非常感兴趣的研究细胞质Esrp 1在维持上皮细胞功能的贡献。
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.