{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["29(1)"],"submitter":["Wu R"],"pubmed_abstract":["While N<sup>6</sup>-methyladenosine (m<sup>6</sup>A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m<sup>6</sup>A modification in mammalian glial development remains unknown. Here, we identify a novel m<sup>6</sup>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<sup>6</sup>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<sup>6</sup>A-dependent manner. Interestingly, we also find that the m<sup>6</sup>A demethylase, Fto, erases the m<sup>6</sup>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<sup>6</sup>A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelination-related neurological diseases."],"journal":["Cell research"],"pagination":["23-41"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6318280"],"repository":["biostudies-literature"],"pubmed_title":["A novel m<sup>6</sup>A reader Prrc2a controls oligodendroglial specification and myelination."],"pmcid":["PMC6318280"],"pubmed_authors":["Wang HL","Liao Y","Yang YG","Zhang J","Sun B","Xiao Y","Wang F","Zhang Q","Yang X","Zhang T","Sun JG","Qi X","Wang S","Gao Y","Wu R","Lai WY","Li A","Chen Y","Ma J","Shu Y","Yuan Z"],"additional_accession":[]},"is_claimable":false,"name":"A novel m<sup>6</sup>A reader Prrc2a controls oligodendroglial specification and myelination.","description":"While N<sup>6</sup>-methyladenosine (m<sup>6</sup>A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m<sup>6</sup>A modification in mammalian glial development remains unknown. Here, we identify a novel m<sup>6</sup>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<sup>6</sup>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<sup>6</sup>A-dependent manner. Interestingly, we also find that the m<sup>6</sup>A demethylase, Fto, erases the m<sup>6</sup>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<sup>6</sup>A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelination-related neurological diseases.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jan","modification":"2024-11-12T18:17:36.538Z","creation":"2019-03-26T22:39:25Z"},"accession":"S-EPMC6318280","cross_references":{"pubmed":["30514900"],"doi":["10.1038/s41422-018-0113-8"]}}