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mA Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2 / 基因组蛋白质组与生物信息学报·英文版
Genomics, Proteomics & Bioinformatics ; (4): 154-168, 2019.
Article in English | WPRIM | ID: wpr-772943
ABSTRACT
N-methyladenosine (mA), catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14, is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However, the roles and precise mechanisms of mA modification in regulating neuronal development and adult neurogenesis remain unclear. Here, we examined the function of Mettl3, the key component of the complex, in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced mA levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neuronal development and skewed the differentiation of aNSCs more toward glial lineage, but also affected the morphological maturation of newborn neurons in the adult brain. mA immunoprecipitation combined with deep sequencing (MeRIP-seq) revealed that mA was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically, mA was present on the transcripts of histone methyltransferase Ezh2, and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively, our results uncover a crosstalk between RNA and histone modifications and indicate that Mettl3-mediated mA modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Brain / RNA, Messenger / Cell Differentiation / Adenosine / Gene Expression Regulation / Cell Biology / Cell Proliferation / Adult Stem Cells / Neurogenesis / Neural Stem Cells Limits: Animals Language: English Journal: Genomics, Proteomics & Bioinformatics Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Brain / RNA, Messenger / Cell Differentiation / Adenosine / Gene Expression Regulation / Cell Biology / Cell Proliferation / Adult Stem Cells / Neurogenesis / Neural Stem Cells Limits: Animals Language: English Journal: Genomics, Proteomics & Bioinformatics Year: 2019 Type: Article