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Posttranscriptional regulation of intestinal epithelial integrity by noncoding RNAs

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Maintenance of the gut epithelial integrity under stressful environments requires epithelial cells to rapidly elicit changes in gene expression patterns to regulate their survival, adapt to stress, and keep epithelial homeostasis. Disruption of the intestinal epithelial integrity occurs commonly in patients with various critical illnesses, leading to the translocation of luminal toxic substances and bacteria to the blood stream. Recently, noncoding RNAs (ncRNAs) have emerged as a novel class of master regulators of gene expression and are fundamentally involved in many aspects of gut mucosal regeneration, protection, and epithelial barrier function. Here, we highlight the roles of several intestinal epithelial tissue‐specific microRNAs, including miR‐222, miR‐29b, miR‐503, and miR‐195, and long ncRNAs such as H19 and SPRY4‐IT1 in the regulation of cell proliferation, apoptosis, migration, and cell‐to‐cell interactions and also further analyze the mechanisms through which ncRNAs and their interactions with RNA‐binding proteins modulate the stability and translation of target mRNAs. WIREs RNA 2017, 8:e1399. doi: 10.1002/wrna.1399 This article is categorized under: Translation > Translation Regulation RNA Turnover and Surveillance > Regulation of RNA Stability RNA in Disease and Development > RNA in Disease
Schematic diagram depicting the regulation of stim1 mRNA stability by miR‐195 interaction with HuR. miRNA‐195 and HuR compete for association with the stim1 3′‐UTR and regulate stim1 mRNA decay in opposite directions. ER, endoplasmic reticulum; PM, plasma membrane; TRPC1, canonical transient receptor potential‐1.
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Model proposed to explain posttranscriptional regulation of intestinal epithelial integrity by noncoding RNAs (ncRNAs). There are two groups of ncRNAs: negative ncRNAs that disrupt the intestinal epithelial integrity, and positive ncRNAs that increase mucosal growth and protect the barrier function. RNA‐binding proteins (RBPs) interact with both negative and positive ncRNA and regulate their biological functions synergistically or antagonistically. Normal intestinal epithelial integrity depends on the balance between positive and negative ncRNAs.
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Schematic diagram of proposed influence of SPRY4‐IT1 upon the epithelial tight junction (TJ) permeability. SPRY4‐IT1 interacts with HuR and forms SPRY4IT1/HuR complex that binds to the mRNAs encoding TJs. SPRY4‐IT1 also directly interacts with the TJ mRNAs. SPRY4‐IT1 and its interaction with HuR enhance the gut barrier function by increasing TJ expression.
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RNA in Disease and Development > RNA in Disease
Translation > Translation Regulation
RNA Turnover and Surveillance > Regulation of RNA Stability

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