The m6A methyltransferase METTL3 cooperates with demethylase ALKBH5 to regulate osteogenic differentiation through NF-κB signaling

Yu, Jinjin; Shen, Lujun; Li, Yanli; Hong, Ming; Zhu, Xinxing; Chu, Maoping

doi:10.1007/s11010-019-03641-5

Cited by 66 publications

(53 citation statements)

References 26 publications

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“…Apart from this, MYD88 gene, a vital upstream regulator of nuclear factor κB (NF-κB) signaling, was methylated by METTL3, followed by activation of NF-κB and repression of osteogenic progression. Meanwhile, the METTL3-mediated osteogenic differentiation tendency could be reversed by demethylase ALKBH5 ( Yu et al, 2020 ). Moreover, silencing METTL3 decreased the osteogenic markers, Smad signaling, and mineralized nodules in preosteoblast MC3T3-E1 cells, indicating the reduction of osteoblast differentiation ( Zhang Y. et al, 2019 ).…”

Section: Rna M 6 a Methylation In Musculoskeletal mentioning

confidence: 99%

Multifaceted Functions and Novel Insight Into the Regulatory Role of RNA N6-Methyladenosine Modification in Musculoskeletal Disorders

Zhang

Liu

et al. 2020

Front. Cell Dev. Biol.

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RNA modifications have emerged as key regulators of transcript expression in diverse physiological and pathological processes. As one of the most prevalent types of RNA modifications, N 6 -methyladenosine (m 6 A) has become the highlight in modulation of various diseases through interfering RNA splicing, translation, nuclear export, and decay. In many cases, the detailed functions of m 6 A in cellular processes and diseases remain unclear. Notably, recent studies have determined the relationship between m 6 A modification and musculoskeletal disorders containing osteosarcoma, osteoarthritis, rheumatoid arthritis, osteoporosis, etc. Herein, this review comprehensively summarizes the recent advances of m 6 A modification in pathogenesis and progression of musculoskeletal diseases. Specifically, the underlying molecular mechanisms, detection technologies, regulatory functions, clinical implications, and future perspectives of m 6 A in musculoskeletal disorders are discussed, with the aim to provide a novel insight into their association.

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Section: Rna M 6 a Methylation In Musculoskeletal mentioning

confidence: 99%

Multifaceted Functions and Novel Insight Into the Regulatory Role of RNA N6-Methyladenosine Modification in Musculoskeletal Disorders

Zhang

Liu

et al. 2020

Front. Cell Dev. Biol.

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“…To the Editor, Nucleotide methylation, notably in the forms of 5methylcytosine (5mC) in DNA and N6-methyladenosine (m 6 A) in mRNA, carries important information for gene regulation [1]. Recent research advances highlight the biological importance of m 6 A methylation as a dynamic and reversible post-transcriptional modification [2]. 5mC DNA methylation, a conserved epigenetic modification along with m 6 A RNA modification, also plays critical roles in fundamental biological processes [3,4].…”

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confidence: 99%

Identification of cross-talk between m6A and 5mC regulators associated with onco-immunogenic features and prognosis across 33 cancer types

et al. 2020

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Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (m 6 A) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between m 6 A and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between m 6 A and 5mC regulators across~11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between m 6 A and 5mC methylation at the multiomic level. Then, we further established m 6 A/5mC epigenetic module eigengenes by combining hub m 6 A/5mC regulators and informed a comprehensive epigenetic state. The model reflected status of the tumor-immune-stromal microenvironment and was able to predict patient survival in the majority of cancer types. Our results lay a solid foundation for epigenetic regulation in human cancer and pave a new road for related therapeutic targets.

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“…However, ZC3H13 depletion impairs self-renewal of mouse embryonic stem cells due to the cells cultured in metastable naive condition [114]. METTL3 depletion potentiates both calcium deposition and alkaline phosphatase activity of mesenchymal stem cells by modulating the expression of MYD required for activating NF-κB, as a repressor of osteogenesis, which uncovers the inhibitory role of METTL3 in osteogenic differentiation [115]. ALKBH5 deteriorates the m 6 A modification of NANOG mRNA to promote its expression in breast cancer stem cells following exposure to hypoxia, which furtherly accelerates cell proliferation and regulates cell differentiation [116].…”

Section: A In Immune Responsementioning

confidence: 92%

Function and evolution of RNA N6-methyladenosine modification

2020

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N6-methyladenosine (m 6 A) is identified as the most prevalent and abundant internal RNA modification, especially within eukaryotic mRNAs, which has attracted much attention in recent years since its importance for regulating gene expression and deciding cell fate. m 6 A modification is installed by RNA methyltransferases METTL3, METTL14 and WTAP (Writers), removed by the demethylases FTO and ALKBH5 (Erasers) and recognized by m 6 A binding proteins, such as YT521-B homology YTH domain-containing proteins (Readers). Accumulating evidence shows that m 6 A RNA methylation participates in almost all aspects of RNA processing, implying an association with important bioprocesses. In this review, we mainly summarize and discuss the functional relevance and importance of m 6 A modification in cellular processes.

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The m6A methyltransferase METTL3 cooperates with demethylase ALKBH5 to regulate osteogenic differentiation through NF-κB signaling

Cited by 66 publications

References 26 publications

Multifaceted Functions and Novel Insight Into the Regulatory Role of RNA N6-Methyladenosine Modification in Musculoskeletal Disorders

Multifaceted Functions and Novel Insight Into the Regulatory Role of RNA N6-Methyladenosine Modification in Musculoskeletal Disorders

Identification of cross-talk between m6A and 5mC regulators associated with onco-immunogenic features and prognosis across 33 cancer types

Function and evolution of RNA N6-methyladenosine modification

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