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Long noncoding RNA uc.230/CUG-binding protein 1 axis sustains intestinal epithelial homeostasis and response to tissue injury

Authors :
Ting-Xi Yu
Sudhakar Kalakonda
Xiangzheng Liu
Naomi Han
Hee K. Chung
Lan Xiao
Jaladanki N. Rao
Tong-Chuan He
Jean-Pierre Raufman
Jian-Ying Wang
Source :
JCI Insight, Vol 7, Iss 19 (2022)
Publication Year :
2022
Publisher :
American Society for Clinical investigation, 2022.

Abstract

Intestinal epithelial integrity is commonly disrupted in patients with critical disorders, but the exact underlying mechanisms are unclear. Long noncoding RNAs transcribed from ultraconserved regions (T-UCRs) control different cell functions and are involved in pathologies. Here, we investigated the role of T-UCRs in intestinal epithelial homeostasis and identified T-UCR uc.230 as a major regulator of epithelial renewal, apoptosis, and barrier function. Compared with controls, intestinal mucosal tissues from patients with ulcerative colitis and from mice with colitis or fasted for 48 hours had increased levels of uc.230. Silencing uc.230 inhibited the growth of intestinal epithelial cells (IECs) and organoids and caused epithelial barrier dysfunction. Silencing uc.230 also increased IEC vulnerability to apoptosis, whereas increasing uc.230 levels protected IECs against cell death. In mice with colitis, reduced uc.230 levels enhanced mucosal inflammatory injury and delayed recovery. Mechanistic studies revealed that uc.230 increased CUG-binding protein 1 (CUGBP1) by acting as a natural decoy RNA for miR-503, which interacts with Cugbp1 mRNA and represses its translation. These findings indicate that uc.230 sustains intestinal mucosal homeostasis by promoting epithelial renewal and barrier function and that it protects IECs against apoptosis by serving as a natural sponge for miR-503, thereby preserving CUGBP1 expression.

Subjects

Subjects :
Gastroenterology
Medicine

Details

Language :
English
ISSN :
23793708
Volume :
7
Issue :
19
Database :
Directory of Open Access Journals
Journal :
JCI Insight
Publication Type :
Academic Journal
Accession number :
edsdoj.32286427e5df489383dffb0553a6911b
Document Type :
article
Full Text :
https://doi.org/10.1172/jci.insight.156612