Transcriptome-wide reprogramming of N6-methyladenosine modification by the mouse microbiome

Wang, Xiaoyun; Li, Yán; Shi, Hailing; Eren, A. Murat; Morozov, Aleksey; He, Chuan; Luo, Guan‐Zheng; Pan, Tao

doi:10.1038/s41422-018-0127-2

Cited by 49 publications

(44 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…39 Recent studies demonstrated that microbiomes had strong effects on m6A modification and expression of m6A 'writers' in mouse brain and intestine. 40 By consulting the literature, we found three intestinal flora metabolites that are most closely related to the development of CRC: Short-chain fatty acids (butyrate), 66 DCA 67 and ursodeoxycholic acid. 68,69 In the present study, we found that butyrate, a classical intestinal microbial metabolite, could decrease the level of m6A and down-regulate the expression of METTL3 and CCNE1 in CRC cells.…”

Section: Discussionmentioning

confidence: 99%

“…Human intestinal microbiota can promote or suppress CRC, not only due to the carcinogenic activities of pathogenic bacterium but also caused by the complex effect of wider microbial community, particularly their metabolites, such as deoxycholic acid (DCA), ursodeoxycholic acid and butyrate . Recent studies demonstrated that microbiomes have strong effects on the m6A modification and METTL3 expression in mouse brain and intestine . However, whether human intestinal microbiota and their metabolites can affect the CRC m6A modification was still unknown.…”

Section: Introductionmentioning

confidence: 99%

“…39 Recent studies demonstrated that microbiomes have strong effects on the m6A modification and METTL3 expression in mouse brain and intestine. 40 However, whether human intestinal microbiota and their metabolites can affect the CRC m6A modification was still unknown. As a classical intestinal microbial metabolite, butyrate is an abundant (up to >10 mmol/L) short-chain fatty acid that is transported into the colonic epithelium and localizes within two subcellular compartments.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner

Zhu

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

m6A modification is the most prevalent RNA modification in eukaryotes. As the critical N6‐methyladenosine (m6A) methyltransferase, the roles of methyltransferase like 3 (METTL3) in colorectal cancer (CRC) are controversial. Here, we confirmed that METTL3, a critical m6A methyltransferase, could facilitate CRC progression in vitro and in vivo. Further, we found METTL3 promoted CRC cell proliferation by methylating the m6A site in 3′‐untranslated region (UTR) of CCNE1 mRNA to stabilize it. Moreover, we found butyrate, a classical intestinal microbial metabolite, could down‐regulate the expression of METTL3 and related cyclin E1 to inhibit CRC development. METTL3 promotes CRC proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner, representing a promising therapeutic strategy for the treatment of CRC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner

Zhu

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…The increase in the expression level of tsRNAs might further control translational machinery in a multitude of ways 51 . In addition, the mouse microbiome can strongly affect host N6-methyladenosine (m 6 A) mRNA modification (m 6 A is an abundant modification in mRNA that regulates multiple aspects of mRNA metabolism 34 ) in a tissue-specific manner, by altering the expression of m 6 A writer and eraser proteins 52 . These intriguing lines of evidence suggest the existence of a complex interplay that links food intake and the gut microbiome to RNA modifications.…”

Section: Box 2 | Inheritance Of Complex Traits From Ancestral Environmentioning

confidence: 99%

Sperm RNA code programmes the metabolic health of offspring

et al. 2019

View full text Add to dashboard Cite

“…However, a complete understanding of mechanisms underlying gut-microbiota-host interactions still remains elusive. Recent reports have suggested that changes in m 6 A levels are associated with inflammatory states 14,34 and very recently, the presence of a microbiota has been suggested to induce changes in epitranscriptomic profiles in the brain, and several other tissues 35 .…”

mentioning

confidence: 99%

Impact of the gut microbiota on the m6A epitranscriptome of mouse cecum and liver

et al. 2020

View full text Add to dashboard Cite

The intestinal microbiota modulates host physiology and gene expression via mechanisms that are not fully understood. Here we examine whether host epitranscriptomic marks are affected by the gut microbiota. We use methylated RNA-immunoprecipitation and sequencing (MeRIP-seq) to identify N6-methyladenosine (m 6 A) modifications in mRNA of mice carrying conventional, modified, or no microbiota. We find that variations in the gut microbiota correlate with m 6 A modifications in the cecum, and to a lesser extent in the liver, affecting pathways related to metabolism, inflammation and antimicrobial responses. We analyze expression levels of several known writer and eraser enzymes, and find that the methyltransferase Mettl16 is downregulated in absence of a microbiota, and one of its target mRNAs, encoding S-adenosylmethionine synthase Mat2a, is less methylated. We furthermore show that Akkermansia muciniphila and Lactobacillus plantarum affect specific m 6 A modifications in mono-associated mice. Our results highlight epitranscriptomic modifications as an additional level of interaction between commensal bacteria and their host.

show abstract

Transcriptome-wide reprogramming of N6-methyladenosine modification by the mouse microbiome

Cited by 49 publications

References 15 publications

Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner

Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner

Sperm RNA code programmes the metabolic health of offspring

Impact of the gut microbiota on the m6A epitranscriptome of mouse cecum and liver

Contact Info

Product

Resources

About