Accession |
PRJCA001128 |
Title |
mRNA Methyltransferase Mettl3 Regulates Neurogenesis and Neuronal Development via Modulating Histone Methyltransferase Ezh2 |
Relevance |
Medical |
Data types |
Raw sequence reads
|
Organisms |
Mus musculus
|
Description |
N6-methyladenosien (m6A), deposited by methyltransferase complex including Mettl3 and Mettl14, is the most abundant RNA modification in messenger RNAs (mRNAs), and involves in diverse biological processes. However, the roles and precise mechanisms of m6A modification regulating neuronal development and adult neurogenesis are unclear. Here, we examined the function of main component Mettl3 in neuronal development and adult neurogenesis. We found that the depletion of Mettl3 significantly reduced m6A levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Furthermore, Mettl3 depletion inhibited neuronal development and skewed the differentiation of aNSCs towards glial lineage. Mettl3 depletion also inhibited the morphological maturation of new born neurons. m6A MeRIP-seq revealed that m6A tags predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically, transcripts of histone methyltransferase Ezh2 contained m6A, and Mettl3 depletion resulted in decreased protein level of Ezh2 and therefore reduced H3K27me3. The overexpression of Ezh2 could rescue the deficits of neurogenesis and neuronal development induced by Mettl3 depletion. Collectively, our results indicated that Mettl3 mediated m6A modification plays important roles in regulating the neurogenesis and neuronal development through modulating Ezh2. |
Sample scope |
Multiisolate |
Release date |
2023-03-10 |
Publication |
PubMed ID |
Article title |
Journal name |
DOI |
Year |
31154015
|
m6A Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2
|
Genomics, Proteomics & Bioinformatics
|
10.1016/j.gpb.2018.12.007
|
2019
|
|
Grants |
Agency |
program |
Grant ID |
Grant title |
National Natural Science Foundation of China (NSFC)
|
General Program
|
31771395
|
|
Ministry of Science and Technology of the People's Republic of China (MOST)
|
|
2018YFA0109700
|
|
|
Submitter |
Yichang
Zhang (zhangyichang@big.ac.cn)
|
Organization |
Beijing Institute of Genomics, Chinese Academy of Sciences |
Submission date |
2018-11-19 |