Open Accessm 6 A mRNA modification maintains colonic epithelial cell homeostasis via NF-κB–mediated antiapoptotic pathway
Author(s) -
Ting Zhang,
Chenbo Ding,
Huifang Chen,
Jun Zhao,
Zhejun Chen,
Baiwen Chen,
Kaiqiong Mao,
Yajuan Hao,
Manolis Roulis,
Hao Xu,
Yuval Kluger,
Qiang Zou,
Youqiong Ye,
Meixiao Zhan,
Richard A. Flavell,
Hua Bing Li
Publication year - 2022
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abl5723
Subject(s) - stem cell , microbiology and biotechnology , apoptosis , homeostasis , inflammatory bowel disease , biology , cell , intestinal mucosa , cancer research , immunology , medicine , pathology , disease , biochemistry
Colonic mucosal barrier dysfunction is one of the major causes of inflammatory bowel disease (IBD). However, the mechanisms underlying mucosal barrier dysfunction are poorly understood.N 6 -methyladenosine (m6 A) mRNA modification is an important modulator of epitranscriptional regulation of gene expression, participating in multiple physiological and pathological processes. However, the function of m6 A modification in colonic epithelial cells and stem cells is unknown. Here, we show that m6 A modification is essential for maintaining the homeostatic self-renewal in colonic stem cells. Specific deletion of the methyltransferase 14 (Mettl14 ) gene in mouse colon resulted in colonic stem cell apoptosis, causing mucosal barrier dysfunction and severe colitis. Mechanistically, we revealed thatMettl14 restricted colonic epithelial cell death by regulating the stability ofNfkbia mRNA and modulating the NF-κB pathway. Our results identified a previously unidentified role for m6 A modification in colonic epithelial cells and stem cells, suggesting that m6 A modification may be a potential therapeutic target for IBD.