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Review
. 2013 Dec;70(23):4463-77.
doi: 10.1007/s00018-013-1379-0. Epub 2013 May 29.

Posttranscriptional regulation by RNA-binding proteins during epithelial-to-mesenchymal transition

Affiliations
Review

Posttranscriptional regulation by RNA-binding proteins during epithelial-to-mesenchymal transition

Luis A Aparicio et al. Cell Mol Life Sci. 2013 Dec.

Abstract

Epithelial-to-mesenchymal transition (EMT), one of the crucial steps for carcinoma cells to acquire invasive capacity, results from the disruption of cell-cell contacts and the acquisition of a motile mesenchymal phenotype. Although the transcriptional events controlling EMT have been extensively studied, in recent years, several posttranscriptional mechanisms have emerged as critical in the regulation of EMT during tumor progression. In this review, we highlight the regulation of posttranscriptional events in EMT by RNA-binding proteins (RBPs). RBPs are responsible for controlling pre-mRNA splicing, capping, and polyadenylation, as well as mRNA export, turnover, localization, and translation. We discuss the most relevant aspects of RBPs controlling the metabolism of EMT-related mRNAs, and describe the implication of novel posttranscriptional mechanisms regulating EMT in response to different signaling pathways. Novel insight into posttranscriptional regulation of EMT by RBPs is uncovering new therapeutic targets in cancer invasion and metastasis.

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Conflict of interest statement

There are no potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Epithelial-to-mesenchymal transition. Epithelial cells (left) are tightly interconnected by E-cadherin at adherent junctions. E-cadherin is linked to the actin cytoskeleton through different catenins. During EMT, E-cadherin can be downregulated by transcriptional repressors (such as Snail, Twist-1, and ZEB1/2), and by posttranslational regulators (such as Hakai). The loss of epithelial markers is accompanied by induction of vimentin, N-cadherin, and fibronectin, by increased levels of nuclear β-catenin, and by the promotion of a mesenchymal phenotype (right)
Fig. 2
Fig. 2
Schematic representation of posttranscriptionally regulated mRNAs by RBPs during EMT. RBPs involved in several posttranscriptional steps include ESRP1, Zeppo1, SF2/ASF (splicing), Sam68 (AS-NMD), ESRP (polyadenylation), hnRNPE1 (translation), TTP, HuR (mRNA turnover). PSF was first described as a splicing factor, although the specific posttranscriptional regulatory action on its mRNA targets remains unclear

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