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M6A mRNA modification is a rheostat to maintain colonic epithelial cell homeostasis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE171423 | GEO | 2022/04/19

REPOSITORIES: GEO

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m6A mRNA modification is a rheostat to maintain colonic epithelial cell homeostasis [scRNA-seq]

Project description:The function of m6A modification in colonic epithelial cells has been validated in our study that depletion of METTL14 in colonic epithelial cells triggers cell death. To further explore the biological effects of m6A deficiency in colonic epithelial cell heterogeneity, we performed single cell RNA-seq of colonic epithelial cells form 2-week-old Mettl14-KO and WT control mice

2022-04-19 | GSE171422 | GEO

m6A mRNA modification is a rheostat to maintain colonic epithelial cell homeostasis [bulkRNA-seq]

Project description:The function of m6A modification in colonic epithelial cells has been validated in our study that depletion of METTL14 in colonic epithelial cells triggers cell death. To further explore the biological effects of m6A deficiency in colonic epithelial cells, we performed RNA sequencing analysis of colonic epithelial cells form 2-week-old Mettl14-KO and WT control mice.The bioinformatic analysis revealed that METTL14 depletion increased the mRNA expression of NF-kB inhibitor Nfkbia, which favored TNF-induced cell death.

2022-04-19 | GSE171421 | GEO

m6A mRNA modification is a rheostat to maintain colonic epithelial cell homeostasis

Project description:m6A mRNA modification is a rheostat to maintain colonic epithelial cell homeostasis

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m6A mRNA modification is a rheostat to maintain colonic epithelial cell homeostasis [scRNA-seq]

Project description:m6A mRNA modification is a rheostat to maintain colonic epithelial cell homeostasis [scRNA-seq]

| PRJNA719513 | ENA

m6A mRNA modification is a rheostat to maintain colonic epithelial cell homeostasis [bulkRNA-seq]

Project description:m6A mRNA modification is a rheostat to maintain colonic epithelial cell homeostasis [bulkRNA-seq]

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m<sup>6</sup>A mRNA modification maintains colonic epithelial cell homeostasis via NF-κB-mediated antiapoptotic pathway.

Project description: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. N6-methyladenosine (m6A) mRNA modification is an important modulator of epitranscriptional regulation of gene expression, participating in multiple physiological and pathological processes. However, the function of m6A modification in colonic epithelial cells and stem cells is unknown. Here, we show that m6A 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 that Mettl14 restricted colonic epithelial cell death by regulating the stability of Nfkbia mRNA and modulating the NF-κB pathway. Our results identified a previously unidentified role for m6A modification in colonic epithelial cells and stem cells, suggesting that m6A modification may be a potential therapeutic target for IBD.

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m6A modification maps of mRNA in colonic epithelial cells from mouse

Project description:We report the application of sequencing technology for high-throughput profiling of mRNA m6A methylation in mice colonic epithelial cells with or without mettl14 deletion. By obtaining over thirty billion bases of sequence from m6A antibody immunoprecipitated mRNA, we generated m6A methylation maps of mouse colonic epithelial cells with or with mettl14 deletion. We find that GsdmC2, GsdmC3, GadmC3 mRNA methylation is robustly decreased in colonic epithelial cells upon mettl14 deletion, leading to the decrease of Gsdmc expression.

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METTL3 protects METTL14 from STUB1-mediated degradation to maintain m6A homeostasis

Project description:N6-Methyladenosine (m6A) is an important RNA modification catalyzed by methyltransferase-like 3 (METTL3) and METTL14. m6A homeostasis mediated by the methyltransferase (MTase) complex plays key roles in various biological processes. However, the mechanism underlying METTL14 protein stability and its role in m6A homeostasis remain elusive. Here, we show that METTL14 stability is regulated by the competitive interaction of METTL3 with the E3 ligase STUB1. STUB1 directly interacts with METTL14 to mediate its ubiquitination at lysine residues K148, K156, and K162 for subsequent degradation, resulting in a significant decrease in total m6A levels. The amino acid regions 450-454 and 464-480 of METTL3 are essential to promote METTL14 stabilization. Changes in STUB1 expression affect METTL14 protein levels, m6A modification and tumorigenesis. Collectively, our findings uncover an ubiquitination mechanism controlling METTL14 protein levels to fine-tune m6A homeostasis. Finally, we present evidence that modulating STUB1 expression to degrade METTL14 could represent a promising therapeutic strategy against cancer.

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Transcriptome Profiling of m6A mRNA Modification in Bovine Mammary Epithelial Cells Treated with Escherichia coli.

Project description:Mastitis is a common disease in dairy cows that is mostly caused by E. coli, and it brings massive losses to the dairy industry. N6-Methyladenosine (m6A), a methylation at the N6 position of RNA adenine, is a type of modification strongly associated with many diseases. However, the role of m6A in mastitis has not been investigated. In this study, we used MeRIP-seq to sequence the RNA of bovine mammary epithelial cells treated with inactivated E. coli for 24 h. In this in vitro infection model, there were 16,691 m6A peaks within 7066 mRNA transcripts in the Con group and 10,029 peaks within 4891 transcripts in the E. coli group. Compared with the Con group, 474 mRNAs were hypermethylated and 2101 mRNAs were hypomethylated in the E. coli group. Biological function analyses revealed differential m6A-modified genes mainly enriched in the MAPK, NF-κB, and TGF-β signaling pathways. In order to explore the relationship between m6A and mRNA expression, combined MeRIP-seq and mRNA-seq analyses revealed 212 genes with concomitant changes in the mRNA expression and m6A modification. This study is the first to present a map of RNA m6A modification in mastitis treated with E. coli, providing a basis for future research.

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Yap/Taz inhibit goblet cell fate to maintain lung epithelial homeostasis

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-08-19 | GSE158307 | GEO