A novel m(6)A reader Prrc2a controls oligodendroglial specification and myelination
文献类型：期刊论文
| 作者 | Wu, Rong; Li, Ang; Sun, Baofa; Sun, Jian-Guang; Zhang, Jinhua; Zhang, Ting; Chen, Yusheng; Xiao, Yujie; Gao, Yuhao; Zhang, Qingyang |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2019 |
| 卷号 | 29期号:1页码:23-41 |
| ISSN号 | 1001-0602 |
| 英文摘要 | While N-6-methyladenosine (m(6)A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m(6)A modification in mammalian glial development remains unknown. Here, we identify a novel m(6)A reader, Prrc2a (Proline rich coiled-coil 2 A), which controls oligodendrocyte specification and myelination. Nestin-Cre-mediated knockout of Prrc2a induces significant hypomyelination, decreased lifespan, as well as locomotive and cognitive defects in a mouse model. Further analyses reveal that Prrc2a is involved in oligodendrocyte progenitor cells (OPCs) proliferation and oligodendrocyte fate determination. Accordingly, oligodendroglial-lineage specific deletion of Prrc2a causes a similar phenotype of Nestin-Cre-mediated deletion. Combining transcriptome-wide RNA-seq, m(6)A-RIP-seq and Prrc2a RIP-seq analysis, we find that Olig2 is a critical downstream target gene of Prrc2a in oligodendrocyte development. Furthermore, Prrc2a stabilizes Olig2 mRNA through binding to a consensus GGACU motif in the 0142 CDS (coding sequence) in an m(6)A-dependent manner. Interestingly, we also find that the m 6 A demethylase, Fto, erases the m(6)A modification of Olig2 mRNA and promotes its degradation. Together, our results indicate that Prrc2a plays an important role in oligodendrocyte specification through functioning as a novel m(6)A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelinationrelated neurological diseases. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/42885]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Beijing Inst Genom, Key Lab Genom & Precis Med, Collaborat Innovat Ctr Genet & Dev, Beijing 100101, Peoples R China 2.Univ Chinese Acad Sci, Sch Life Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China 4.Beijing Jiaotong Univ, Coll Life Sci & Bioengn, Beijing, Peoples R China 5.Beijing Inst Basic Med Sci, Brain Sci Ctr, Beijing 100850, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Rong,Li, Ang,Sun, Baofa,et al. A novel m(6)A reader Prrc2a controls oligodendroglial specification and myelination[J]. CELL RESEARCH,2019,29(1):23-41. |
| APA | Wu, Rong.,Li, Ang.,Sun, Baofa.,Sun, Jian-Guang.,Zhang, Jinhua.,...&Yuan, Zengqiang.(2019).A novel m(6)A reader Prrc2a controls oligodendroglial specification and myelination.CELL RESEARCH,29(1),23-41. |
| MLA | Wu, Rong,et al."A novel m(6)A reader Prrc2a controls oligodendroglial specification and myelination".CELL RESEARCH 29.1(2019):23-41. |
入库方式： OAI收割
来源：生态环境研究中心
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