Competitive Binding of Occludin mRNA to CUG-binding Protein 1 and HuR Regulates Its Translation and Epithelial Barrier Function

The AP-1 transcription factor JunD is highly expressed in intestinal epithelial cells, but its exact role in maintaining the integrity of intestinal epithelial barrier remains unknown. The tight junction (TJ) protein zonula occludens (ZO)-1 links the intracellular domain of TJ-transmembrane proteins occludin, claudins, and junctional adhesion molecules to many cytoplasmic proteins and the actin cytoskeleton and is crucial for assembly of the TJ complex. Here, we show that JunD negatively regulates expression of ZO-1 and is implicated in the regulation of intestinal epithelial barrier function. Increased JunD levels by ectopic overexpression of the junD gene or by depleting cellular polyamines repressed ZO-1 expression and increased epithelial paracellular permeability. JunD regulated ZO-1 expression at the levels of transcription and translation. Transcriptional repression of ZO-1 by JunD was mediated through cAMP response element-binding protein-binding site within its proximal region of the ZO-1-promoter, whereas induced JunD inhibited ZO-1 mRNA translation by enhancing the interaction of the ZO-1 3′-untranslated region with RNA-binding protein T cell-restricted intracellular antigen 1-related protein. These results indicate that JunD is a biological suppressor of ZO-1 expression in intestinal epithelial cells and plays a critical role in maintaining epithelial barrier function.

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291 LncRNA Spry4-it1 Modulates Tight Junction Expression and Epithelial Barrier Function Through Interaction With the RNA-Binding Protein HuR

Gastroenterology ◽

10.1016/s0016-5085(14)60250-x ◽

2014 ◽

Vol 146 (5) ◽

pp. S-69

Author(s):

Lan Xiao ◽

Rao N. Jaladanki ◽

Myriam Gorospe ◽

Jian-Ying Wang

Keyword(s):

Tight Junction ◽

Barrier Function ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Epithelial Barrier ◽

Epithelial Barrier Function

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Tu1741 RNA-Binding Protein HuR Enhances Translation of E-Cadherin and Modulates Epithelial Barrier Function

Gastroenterology ◽

10.1016/s0016-5085(13)63104-2 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-834-S-835

Author(s):

Tingxi Yu ◽

Bei-Lin Gu ◽

Wei Cai

Keyword(s):

Barrier Function ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Epithelial Barrier ◽

Epithelial Barrier Function ◽

E Cadherin

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H19Long Noncoding RNA Regulates Intestinal Epithelial Barrier Function via MicroRNA 675 by Interacting with RNA-Binding Protein HuR

Molecular and Cellular Biology ◽

10.1128/mcb.01030-15 ◽

2016 ◽

Vol 36 (9) ◽

pp. 1332-1341 ◽

Cited By ~ 52

Author(s):

Tongtong Zou ◽

Suraj K. Jaladanki ◽

Lan Liu ◽

Lan Xiao ◽

Hee Kyoung Chung ◽

...

Keyword(s):

Barrier Function ◽

Noncoding Rna ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Epithelial Barrier Function ◽

E Cadherin

The disruption of the intestinal epithelial barrier function occurs commonly in various pathologies, but the exact mechanisms responsible are unclear. TheH19long noncoding RNA (lncRNA) regulates the expression of different genes and has been implicated in human genetic disorders and cancer. Here, we report thatH19plays an important role in controlling the intestinal epithelial barrier function by serving as a precursor for microRNA 675 (miR-675).H19overexpression increased the cellular abundance of miR-675, which in turn destabilized and repressed the translation of mRNAs encoding tight junction protein ZO-1 and adherens junction E-cadherin, resulting in the dysfunction of the epithelial barrier. Increasing the level of the RNA-binding protein HuR in cells overexpressingH19prevented the stimulation of miR-675 processing fromH19, promoted ZO-1 and E-cadherin expression, and restored the epithelial barrier function to a nearly normal level. In contrast, the targeted deletion of HuR in intestinal epithelial cells enhanced miR-675 production in the mucosa and delayed the recovery of the gut barrier function after exposure to mesenteric ischemia/reperfusion. These results indicate thatH19interacts with HuR and regulates the intestinal epithelial barrier function via theH19-encoded miR-675 by altering ZO-1 and E-cadherin expression posttranscriptionally.

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