The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events.
The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events.
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DOI：
10.4161/rna.6.5.9606
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发表时间：
2009-11
期刊：
影响因子：
4.1
通讯作者：
Carstens RP
中科院分区：
文献类型：
--
作者：
Warzecha CC;Shen S;Xing Y;Carstens RP
细胞类型和组织特异性的选择性剪接事件受组合控制，既包括丰富的RNA结合蛋白，也包括那些具有更离散表达和特殊功能的蛋白。上皮剪接调节蛋白1和2(ESRP1和ESRP2)是新近发现的上皮特异的RNA结合蛋白，可促进FGFR2、ENAH、CD44和CTNND1转录本上皮变异体的剪接。为了在ESRPs的调控下对更大的剪接事件进行分类，我们使用剪接敏感的Affymetrix Exon ST1.0阵列描述了RNA干扰介导的ESRP1和ESRP2表达下调在人类上皮细胞系中诱导的剪接变化。对微阵列数据的分析导致识别出100多个候选ESRP调控的剪接事件。我们能够通过RT-PCR独立验证这些靶标中的38个。ESRP调控的事件包括所有已知类型的选择性剪接事件，最突出的是选择性盒式外显子和导致选择性3‘末端外显子的剪接事件。重要的是，许多这些受调控的剪接事件发生在基因转录本中，这些转录本编码的蛋白质在肌动蛋白细胞骨架组织、细胞-细胞黏附、细胞极性和细胞迁移的调节中发挥着众所周知的作用。总之，这项工作揭示了在上皮细胞和间充质细胞中差异剪接的一系列新的转录本，这意味着协调的选择性剪接在确定细胞类型的同一性中起着关键作用。这些结果进一步确立了ESRP1和ESRP2作为上皮剪接调控网络的全球调节者。
Cell-type and tissue-specific alternative splicing events are regulated by combinatorial control involving both abundant RNA binding proteins as well as those with more discrete expression and specialized functions. Epithelial Splicing Regulatory Proteins 1 and 2 (ESRP1 and ESRP2) are recently discovered epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the FGFR2, ENAH, CD44 and CTNND1 transcripts. To catalogue a larger set of splicing events under the regulation of the ESRPs we profiled splicing changes induced by RNA interference-mediated knockdown of ESRP1 and ESRP2 expression in a human epithelial cell line using the splicing sensitive Affymetrix Exon ST1.0 Arrays. Analysis of the microarray data resulted in the identification of over a hundred candidate ESRP regulated splicing events. We were able to independently validate 38 of these targets by RT-PCR. The ESRP regulated events encompass all known types of alternative splicing events, most prominent being alternative cassette exons and splicing events leading to alternative 3' terminal exons. Importantly, a number of these regulated splicing events occur in gene transcripts that encode proteins with well-described roles in the regulation of actin cytoskeleton organization, cell-cell adhesion, cell polarity and cell migration. In sum, this work reveals a novel list of transcripts differentially spliced in epithelial and mesenchymal cells, implying that coordinated alternative splicing plays a critical role in determination of cell type identity. These results further establish ESRP1 and ESRP2 as global regulators of an epithelial splicing regulatory network.
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DOI：
10.1083/jcb.200712086
发表时间：
2008-09-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hirano M;Hashimoto S;Yonemura S;Sabe H;Aizawa S
通讯作者：
Aizawa S
影响因子：
4.5
作者：
Hung, Lee-Hsueh;Heiner, Monika;Bindereif, Albrecht
通讯作者：
Bindereif, Albrecht
影响因子：
7.5
作者：
Hartmann, Britta;Valcarcel, Juan
通讯作者：
Valcarcel, Juan
影响因子：
3.7
作者：
Gosens, Ilse;Sessa, Alessandro;Roepman, Ronald
通讯作者：
Roepman, Ronald
影响因子：
8
作者：
Dow, L. E.;Kauffman, J. S.;Humbert, P. O.
通讯作者：
Humbert, P. O.