2. Academic Validation
  3. A novel m6A reader Prrc2a controls oligodendroglial specification and myelination

A novel m6A reader Prrc2a controls oligodendroglial specification and myelination

  • Cell Res. 2019 Jan;29(1):23-41. doi: 10.1038/s41422-018-0113-8.
Rong Wu 1,  Ang Li 2 3,  Baofa Sun 2 3,  Jian-Guang Sun 1 3 4,  Jinhua Zhang 5,  Ting Zhang 2 3,  Yusheng Chen 2 3,  Yujie Xiao 6,  Yuhao Gao 1 3 4,  Qingyang Zhang 2 3,  Jun Ma 1,  Xin Yang 2 3,  Yajin Liao 1,  Wei-Yi Lai 3 7,  Xiaolong Qi 1 4,  Shukun Wang 1,  Yousheng Shu 6,  Hai-Lin Wang 7,  Fengchao Wang 8,  Yun-Gui Yang 9 10 11,  Zengqiang Yuan 12 13
Affiliations

Affiliations

  • 1 The Brain Science Center, Beijing Institute of Basic Medical Sciences, 100850, Beijing, China.
  • 2 Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101, Beijing, China.
  • 3 School of Life Science, University of Chinese Academy of Sciences, 100049, Beijing, China.
  • 4 Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
  • 5 The College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, China.
  • 6 State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, School of Brain and Cognitive Sciences, the Collaborative Innovation Center for Brain Science, Beijing Normal University, 100875, Beijing, China.
  • 7 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, 100085, Beijing, China.
  • 8 National Institute of Biological Sciences, Beijing, China. wangfengchao@nibs.ac.cn.
  • 9 Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101, Beijing, China. ygyang@big.ac.cn.
  • 10 School of Life Science, University of Chinese Academy of Sciences, 100049, Beijing, China. ygyang@big.ac.cn.
  • 11 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101, Beijing, China. ygyang@big.ac.cn.
  • 12 The Brain Science Center, Beijing Institute of Basic Medical Sciences, 100850, Beijing, China. zqyuan@bmi.ac.cn.
  • 13 Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China. zqyuan@bmi.ac.cn.
PMID: 30514900 DOI: 10.1038/s41422-018-0113-8
Abstract

While N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m6A modification in mammalian glial development remains unknown. Here, we identify a novel m6A 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, m6A-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 OLIG2 CDS (coding sequence) in an m6A-dependent manner. Interestingly, we also find that the m6A demethylase, Fto, erases the m6A 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 m6A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelination-related neurological diseases.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z