An ESRP-regulated splicing programme is abrogated during the epithelial-mesenchymal transition
An ESRP-regulated splicing programme is abrogated during the epithelial-mesenchymal transition
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DOI：
10.1038/emboj.2010.195
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发表时间：
2010-10-06
期刊：
影响因子：
11.4
通讯作者：
Carstens, Russ P.
中科院分区：
文献类型：
--
作者：
Warzecha, Claude C.;Jiang, Peng;Carstens, Russ P.
选择性剪接通过多种RNA结合蛋白的活性实现转录后基因表达程序的协调变化。上皮剪接调节蛋白1和2（ESRP 1和ESRP 2）是上皮-间充质转化（EMT）过程中细胞类型特异性的转录本剪接调节因子。为了定义在EMT期间调节的选择性剪接的综合方案，我们在具有细胞-细胞粘附、极性和迁移功能的众多基因内鉴定了数百个选择性剪接事件的广泛的ESRP调节的剪接网络。这种整体ESRP调节的上皮剪接程序的丧失诱导在EMT期间观察到的细胞形态的表型变化。这种剪接特征的组分提供了可用于表征EMT的新分子标记。生物信息学和实验方法揭示了一个高亲和力的ESRP结合基序和一个预测的RNA图谱，管理他们的活动。这项工作将ESRP确定为复杂的选择性剪接网络的协调者，该网络为基因表达变化添加了一个重要的转录后层，该变化是发育和疾病期间上皮-间充质转变的基础。The EMBO Journal（2010）29，3286-3300. doi：10.1038/daj.2010.195; 2010年8月13日在线发布
Alternative splicing achieves coordinated changes in post-transcriptional gene expression programmes through the activities of diverse RNA-binding proteins. Epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) are cell-type-specific regulators of transcripts that switch splicing during the epithelial-mesenchymal transition (EMT). To define a comprehensive programme of alternative splicing that is regulated during the EMT, we identified an extensive ESRP-regulated splicing network of hundreds of alternative splicing events within numerous genes with functions in cell-cell adhesion, polarity, and migration. Loss of this global ESRP-regulated epithelial splicing programme induces the phenotypic changes in cell morphology that are observed during the EMT. Components of this splicing signature provide novel molecular markers that can be used to characterize the EMT. Bioinformatics and experimental approaches revealed a high-affinity ESRP-binding motif and a predictive RNA map that governs their activity. This work establishes the ESRPs as coordinators of a complex alternative splicing network that adds an important post-transcriptional layer to the changes in gene expression that underlie epithelial-mesenchymal transitions during development and disease. The EMBO Journal (2010) 29, 3286-3300. doi:10.1038/emboj.2010.195; Published online 13 August 2010