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Cited by 366RNA modifications and cancerNeurogenesis and neuroplasticity mechanismsRNA regulation and disease

A novel m6A reader Prrc2a controls oligodendroglial specification and myelination

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Wu, Rong, Li, Ang, Sun, Baofa, Sun, Jian-Guang, Zhang, Jinhua, Zhang, Ting, Chen, Yusheng, Xiao, Yujie +13 more·2019·Cell Research
DOI 10.1038/s41422-018-0113-8PMC PMC6318280
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Abstract

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 Olig2 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 hypomyelination-related neurological diseases.

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  • This result is consistent with the previous observation that deficiency in PRRC2A reduces the oligodendroglia population in the brain and induces hypomyelination, which leads to impaired locomotive and cognitive functions.

    “This result is consistent with the previous observation that deficiency in PRRC2A reduces the oligodendroglia population in the brain and induces hypomyelination, which leads to an impaired locomotive and cognitive functions [74–76].”

    From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [74]

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Authors
Wu, R., Li, A., Sun, B., Sun, J.-G., Zhang, J., Zhang, T., Chen, Y., Xiao, Y., Gao, Y., Zhang, Q., Ma, J., Yang, X., Liao, Y., Lai, W.-Y., Qi, X., Wang, S., Shu, Y., Wang, H.-L., Wang, F., Yang, Y.-G., & Yuan, Z.
Affiliations
  • Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences (CN)
  • Chinese Academy of Sciences (CN)
  • Beijing Jiaotong University (CN)
  • Beijing Normal University (CN)
  • National Institute of Biological Sciences, Beijing (CN)
Corresponding author
  • Wang, Fengchao
  • Yang, Yun-Gui
  • Yuan, Zengqiang
ORCID
Venue
Cell Research
Publisher
Springer Science and Business Media LLC
Published
2018-12-04
Volume
29
Issue
1
Pages
23-41
ISSN
  • 1001-0602 (ISSN-L)
  • 1748-7838
DOI
10.1038/s41422-018-0113-8
PMC
PMC6318280
OpenAlex
W2902945209
Cited by
366
References
15
Citations by year
2026: 22 · 2025: 44 · 2024: 51 · 2023: 70 · 2022: 71 · 2021: 56 · 2020: 38 · 2019: 14
FWCI
9.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81125010, 31670824, 31430022, 2016YFC0900300, 81630026, 81030025, 31625016, 2017SHZDZX01)
  • China Postdoctoral Science Foundation (2017SHZDZX01)
  • National Key Research and Development Program of China (2016YFC0900300, 2017SHZDZX01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
m6A reader, N6-methyladenosine, myelination, hypomyelination, oligodendrocyte precursor cells, Olig2, mRNA stability, FTO demethylase, mRNA degradation, glial development, cognitive defects
MeSH terms
Oligodendrocyte Transcription Factor 2, Adenosine, Animals, Cell Differentiation, Cells, Cultured, Mice, Transgenic, Myelin Sheath, Oligodendroglia, Mice, Neurogenesis, Neural Stem Cells

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