Regulation of Intestinal Epithelial Barrier Function by Long Noncoding RNA uc.173 through Interaction with MicroRNA 29b
The 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 no...
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Published in | Molecular and cellular biology Vol. 38; no. 13 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Taylor & Francis
01.07.2018
American Society for Microbiology |
Subjects | |
Online Access | Get full text |
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Summary: | The 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Citation Wang J-Y, Cui Y-H, Xiao L, Chung HK, Zhang Y, Rao JN, Gorospe M, Wang J-Y. 2018. Regulation of intestinal epithelial barrier function by long noncoding RNA uc.173 through interaction with microRNA 29b. Mol Cell Biol 38:e00010-18. https://doi.org/10.1128/MCB.00010-18. Present address: Jun-Yao Wang, Department of Gastroenterology, People's Hospital, Peking University School of Medicine, Beijing, People's Republic of China; Yu-Hong Cui, Department of Histology and Embryology, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China. |
ISSN: | 1098-5549 0270-7306 1098-5549 |
DOI: | 10.1128/MCB.00010-18 |