ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing.
ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing.
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DOI：
10.1016/j.molcel.2009.01.025
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发表时间：
2009-03-13
期刊：
影响因子：
16
通讯作者：
Carstens, Russ P.
中科院分区：
文献类型：
--
作者：
Warzecha, Claude C.;Sato, Trey K.;Nabet, Behnam;Hogenesch, John B.;Carstens, Russ P.
成纤维细胞生长因子受体2(FGFR2)的上皮型和间叶型的细胞类型特异性表达分别是通过严格调控相互排斥的外显子IIIb和IIIc实现的。利用基于细胞的cDNA表达筛选的新应用，我们鉴定了两个平行上皮细胞类型特异的RNA结合蛋白，它们是FGFR2剪接的重要调节因子。在表达FGFR2-IIIc的细胞中异位表达任何一种蛋白都会导致内源性FGFR2剪接切换到上皮亚型。相反，在表达FGFR2-IIIb的细胞中，通过RNA干扰抑制这两种因子会导致从上皮细胞向间充质细胞亚型的转换。这些因子还调节CD44、p120-catenin(CTNND1)和hMena(ENAH)的剪接，这三个转录本在上皮向间充质转化(EMT)过程中经历剪接的变化。这些研究表明，上皮剪接调控蛋白1和2(ESRP1和ESRP2)是上皮细胞类型特异性剪接程序的协调者。
Cell type-specific expression of epithelial and mesenchymal isoforms of Fibroblast Growth Factor Receptor 2 (FGFR2) is achieved through tight regulation of mutually exclusive exons IIIb and IIIc, respectively. Using a novel application of cell-based cDNA expression screening we identified two paralogous epithelial cell type-specific RNA binding proteins that are essential regulators of FGFR2 splicing. Ectopic expression of either protein in cells that express FGFR2-IIIc caused a switch in endogenous FGFR2 splicing to the epithelial isoform. Conversely, knockdown of both factors in cells that express FGFR2-IIIb by RNA interference caused a switch from the epithelial to mesenchymal isoform. These factors also regulate splicing of CD44, p120-Catenin (CTNND1), and hMena (ENAH); three transcripts that undergo changes in splicing during the epithelial to mesenchymal transition (EMT). These studies suggest that Epithelial Splicing Regulatory Proteins 1 and 2 (ESRP1 and ESRP2) are coordinators of an epithelial cell type-specific splicing program.
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