Regulation of intestinal epithelial barrier function by long noncoding RNA uc.173 through interaction with microRNA 29b
JournalMolecular and Cellular Biology
PublisherAmerican Society for Microbiology
MetadataShow full item record
AbstractThe mammalian intestinal epithelium establishes a selectively permeable barrier that supports nutrient absorption and prevents intrusion by noxious luminal substances and microbiota. The effectiveness and integrity of the barrier function are tightly regulated via well-controlled mechanisms. Long noncoding RNAs transcribed from ultraconserved regions (T-UCRs) control diverse cellular processes, but their roles in the regulation of gut permeability remain largely unknown. Here we report that the T-UCR uc.173 enhances intestinal epithelial barrier function by antagonizing microRNA 29b (miR-29b). Decreasing the levels of uc.173 by gene silencing led to dysfunction of the intestinal epithelial barrier in cultured cells and increased the vulnerability of the gut barrier to septic stress in mice. uc.173 specifically stimulated translation of the tight junction (TJ) claudin-1 (CLDN1) by associating with miR-29b rather than by binding directly to CLDN1 mRNA. uc.173 acted as a natural decoy RNA for miR-29b, which interacts with CLDN1 mRNA via the 3= untranslated region and represses its translation. Ectopically expressed uc.173 abolished the association of miR-29b with CLDN1 mRNA and restored claudin-1 expression to normal levels in cells overexpressing miR-29b, thus rescuing the barrier function. These results highlight a novel function of uc.173 in controlling gut permeability and define a mechanism by which uc.173 stimulates claudin-1 translation, by decreasing the availability of miR-29b to CLDN1 mRNA. Copyright 2018 American Society for Microbiology.
SponsorsThis work was supported by Merit Review Awards (to Jian-Ying Wang and J. N. Rao) from the U.S. Department of Veterans Affairs, grants from the National Institutes of Health (DK57819, DK61972, and DK68491, to Jian-Ying Wang), and funding from the National Institute on Aging Intramural Research Program, NIH (to M. Gorospe).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85048656087&doi=10.1128%2fMCB.00010-18&partnerID=40&md5=a51d9953299e940b9f6cb9dc97cbf6f6; http://hdl.handle.net/10713/9298
- Long Noncoding RNA uc.173 Promotes Renewal of the Intestinal Mucosa by Inducing Degradation of MicroRNA 195.
- Authors: Xiao L, Wu J, Wang JY, Chung HK, Kalakonda S, Rao JN, Gorospe M, Wang JY
- Issue date: 2018 Feb
- Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins.
- Authors: Xiao L, Rao JN, Cao S, Liu L, Chung HK, Zhang Y, Zhang J, Liu Y, Gorospe M, Wang JY
- Issue date: 2016 Feb 15
- MicroRNA regulation of intestinal epithelial tight junction permeability.
- Authors: Ye D, Guo S, Al-Sadi R, Ma TY
- Issue date: 2011 Oct
- MiR-34c and PlncRNA1 mediated the function of intestinal epithelial barrier by regulating tight junction proteins in inflammatory bowel disease.
- Authors: Chen T, Xue H, Lin R, Huang Z
- Issue date: 2017 Apr 22
- Reduced Mucosa-associated Butyricicoccus Activity in Patients with Ulcerative Colitis Correlates with Aberrant Claudin-1 Expression.
- Authors: Devriese S, Eeckhaut V, Geirnaert A, Van den Bossche L, Hindryckx P, Van de Wiele T, Van Immerseel F, Ducatelle R, De Vos M, Laukens D
- Issue date: 2017 Feb