Genome-Wide Activities of RNA Binding Proteins That Regulate Cellular Changes in the Epithelial to Mesenchymal Transition (EMT)
Genome-Wide Activities of RNA Binding Proteins That Regulate Cellular Changes in the Epithelial to Mesenchymal Transition (EMT)
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DOI：
10.1007/978-1-4939-1221-6_8
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发表时间：
2014-01-01
期刊：
影响因子：
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通讯作者：
Carstens, Russ P.
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文献类型：
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作者：
Bebee, Thomas W.;Cieply, Benjamin W.;Carstens, Russ P.
上皮-间充质转化（EMT）和反向间充质-上皮转化（MET）是发育保守的过程，对于发育中的胚胎和器官的模式化至关重要。EMT/MET进一步用于伤口愈合，但它们也可能被癌细胞劫持以促进肿瘤进展和转移。控制这些过程的分子途径历来集中在转录调控和控制它们的网络上。事实上，转录变化的全球概况分析提供了大量信息，这些网络是如何调节的，下游目标，以及全球转录组改变的功能后果。然而，最近的证据表明，在EMT/MET期间，细胞的转录后景观也发生了显着变化，并导致细胞行为和表型的变化。虽然EMT生物学这方面的研究仍处于起步阶段，但最近的进展是通过鉴定几种在EMT期间调节剪接、多聚腺苷酸化、mRNA稳定性和翻译控制的RNA结合蛋白（RBP）来实现的。这一章的重点是全球影响的限制性商业惯例，调节mRNA的成熟，以及概述了几个关键的转录后变化的功能影响EMT期间。越来越多的证据表明RBP参与EMT过程中的细胞转化，强调了转录和转录后变化的协调调节对于EMT至关重要。此外，这些事件的新发现将描绘EMT/MET期间转录组的更详细的图像，并为治疗人类疾病提供新的分子靶点。
The epithelial to mesenchymal transition (EMT) and reverse mesenchymal to epithelial transition (MET) are developmentally conserved processes that are essential for patterning of developing embryos and organs. The EMT/MET are further utilized in wound healing, but they can also be hijacked by cancer cells to promote tumor progression and metastasis. The molecular pathways governing these processes have historically focused on the transcriptional regulation and networks that control them. Indeed, global profiling of transcriptional changes has provided a wealth of information into how these networks are regulated, the downstream targets, and functional consequence of alterations to the global transcriptome. However, recent evidence has revealed that the posttranscriptional landscape of the cell is also dramatically altered during the EMT/MET and contributes to changes in cell behavior and phenotypes. While studies of this aspect of EMT biology are still in their infancy, recent progress has been achieved by the identification of several RNA binding proteins (RBPs) that regulate splicing, polyadenylation, mRNA stability, and translational control during EMT. This chapter focuses on the global impact of RBPs that regulate mRNA maturation as well as outlines the functional impact of several key posttranscriptional changes during the EMT. The growing evidence of RBP involvement in the cellular transformation during EMT underscores that a coordinated regulation of both transcriptional and posttranscriptional changes is essential for EMT. Furthermore, new discoveries into these events will paint a more detailed picture of the transcriptome during the EMT/MET and provide novel molecular targets for treatment of human diseases.