m6A Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2

Publication date: Available online 30 May 2019Source: Genomics, Proteomics & BioinformaticsAuthor(s): Junchen Chen, Yi-Chang Zhang, Chunmin Huang, Hui Shen, Baofa Sun, Xuejun Cheng, Yu-Jie Zhang, Yun-Gui Yang, Qiang Shu, Ying Yang, Xuekun LiAbstractN6-methyladenosine (m6A), 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 m6A 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 m6A 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 towards glial lineage, but also affected the morphological maturation of newborn neurons in the adult brain. m6A immunoprecipitation combined with deep sequencing (MeRIP-seq) revealed that m6A was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically, m6A 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 developme...
Source: Genomics, Proteomics and Bioinformatics - Category: Bioinformatics Source Type: research