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Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins

Epithelial cells line the intestinal mucosa and form an important barrier to a wide array of noxious substances in the lumen. Disruption of the barrier integrity occurs commonly in various pathologies. Long noncoding RNAs (lncRNAs) control diverse biological processes, but little is known about the...

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Autores principales: Xiao, Lan, Rao, Jaladanki N., Cao, Shan, Liu, Lan, Chung, Hee Kyoung, Zhang, Yun, Zhang, Jennifer, Liu, Yulan, Gorospe, Myriam, Wang, Jian-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750922/
https://www.ncbi.nlm.nih.gov/pubmed/26680741
http://dx.doi.org/10.1091/mbc.E15-10-0703
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author Xiao, Lan
Rao, Jaladanki N.
Cao, Shan
Liu, Lan
Chung, Hee Kyoung
Zhang, Yun
Zhang, Jennifer
Liu, Yulan
Gorospe, Myriam
Wang, Jian-Ying
author_facet Xiao, Lan
Rao, Jaladanki N.
Cao, Shan
Liu, Lan
Chung, Hee Kyoung
Zhang, Yun
Zhang, Jennifer
Liu, Yulan
Gorospe, Myriam
Wang, Jian-Ying
author_sort Xiao, Lan
collection PubMed
description Epithelial cells line the intestinal mucosa and form an important barrier to a wide array of noxious substances in the lumen. Disruption of the barrier integrity occurs commonly in various pathologies. Long noncoding RNAs (lncRNAs) control diverse biological processes, but little is known about the role of lncRNAs in regulation of the gut permeability. Here we show that the lncRNA SPRY4-IT1 regulates the intestinal epithelial barrier function by altering expression of tight junction (TJ) proteins. SPRY4-IT1 silencing led to dysfunction of the epithelial barrier in cultured cells by decreasing the stability of mRNAs encoding TJ proteins claudin-1, claudin-3, occludin, and JAM-1 and repressing their translation. In contrast, increasing the levels of SPRY4-IT1 in the intestinal mucosa protected the gut barrier in mice exposed to septic stress by increasing the abundance of TJ proteins. SPRY4-IT1 directly interacted with TJ mRNAs, and this process was enhanced through the association with the RNA-binding protein HuR. Of interest, the intestinal mucosa from patients with increased gut permeability exhibited a decrease in the levels of SPRY4-IT1. These findings highlight a novel role for SPRY4-IT1 in controlling the intestinal epithelial barrier and define a mechanism by which SPRY4-IT1 modulates TJ expression by altering the stability and translation of TJ mRNAs.
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spelling pubmed-47509222016-04-30 Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins Xiao, Lan Rao, Jaladanki N. Cao, Shan Liu, Lan Chung, Hee Kyoung Zhang, Yun Zhang, Jennifer Liu, Yulan Gorospe, Myriam Wang, Jian-Ying Mol Biol Cell Articles Epithelial cells line the intestinal mucosa and form an important barrier to a wide array of noxious substances in the lumen. Disruption of the barrier integrity occurs commonly in various pathologies. Long noncoding RNAs (lncRNAs) control diverse biological processes, but little is known about the role of lncRNAs in regulation of the gut permeability. Here we show that the lncRNA SPRY4-IT1 regulates the intestinal epithelial barrier function by altering expression of tight junction (TJ) proteins. SPRY4-IT1 silencing led to dysfunction of the epithelial barrier in cultured cells by decreasing the stability of mRNAs encoding TJ proteins claudin-1, claudin-3, occludin, and JAM-1 and repressing their translation. In contrast, increasing the levels of SPRY4-IT1 in the intestinal mucosa protected the gut barrier in mice exposed to septic stress by increasing the abundance of TJ proteins. SPRY4-IT1 directly interacted with TJ mRNAs, and this process was enhanced through the association with the RNA-binding protein HuR. Of interest, the intestinal mucosa from patients with increased gut permeability exhibited a decrease in the levels of SPRY4-IT1. These findings highlight a novel role for SPRY4-IT1 in controlling the intestinal epithelial barrier and define a mechanism by which SPRY4-IT1 modulates TJ expression by altering the stability and translation of TJ mRNAs. The American Society for Cell Biology 2016-02-15 /pmc/articles/PMC4750922/ /pubmed/26680741 http://dx.doi.org/10.1091/mbc.E15-10-0703 Text en © 2016 Xiao et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Xiao, Lan
Rao, Jaladanki N.
Cao, Shan
Liu, Lan
Chung, Hee Kyoung
Zhang, Yun
Zhang, Jennifer
Liu, Yulan
Gorospe, Myriam
Wang, Jian-Ying
Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins
title Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins
title_full Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins
title_fullStr Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins
title_full_unstemmed Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins
title_short Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins
title_sort long noncoding rna spry4-it1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750922/
https://www.ncbi.nlm.nih.gov/pubmed/26680741
http://dx.doi.org/10.1091/mbc.E15-10-0703
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