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m6A mRNA Methylation Is Essential for Oligodendrocyte Maturation and CNS Myelination.
Neuron ( IF 14.7 ) Pub Date : 2019-12-31 , DOI: 10.1016/j.neuron.2019.12.013
Huan Xu 1 , Yulia Dzhashiashvili 1 , Ankeeta Shah 2 , Rejani B Kunjamma 1 , Yi-Lan Weng 3 , Benayahu Elbaz 1 , Qili Fei 4 , Joshua S Jones 1 , Yang I Li 5 , Xiaoxi Zhuang 6 , Guo-Li Ming 3 , Chuan He 4 , Brian Popko 1
Affiliation  

The molecular mechanisms that govern the maturation of oligodendrocyte lineage cells remain unclear. Emerging studies have shown that N6-methyladenosine (m6A), the most common internal RNA modification of mammalian mRNA, plays a critical role in various developmental processes. Here, we demonstrate that oligodendrocyte lineage progression is accompanied by dynamic changes in m6A modification on numerous transcripts. In vivo conditional inactivation of an essential m6A writer component, METTL14, results in decreased oligodendrocyte numbers and CNS hypomyelination, although oligodendrocyte precursor cell (OPC) numbers are normal. In vitro Mettl14 ablation disrupts postmitotic oligodendrocyte maturation and has distinct effects on OPC and oligodendrocyte transcriptomes. Moreover, the loss of Mettl14 in oligodendrocyte lineage cells causes aberrant splicing of myriad RNA transcripts, including those that encode the essential paranodal component neurofascin 155 (NF155). Together, our findings indicate that dynamic RNA methylation plays an important regulatory role in oligodendrocyte development and CNS myelination.

中文翻译:

m6A mRNA 甲基化对于少突胶质细胞成熟和 CNS 髓鞘形成至关重要。

控制少突胶质细胞谱系细胞成熟的分子机制仍不清楚。新兴研究表明,N6-甲基腺苷 (m6A) 是哺乳动物 mRNA 最常见的内部 RNA 修饰,在各种发育过程中起着关键作用。在这里,我们证明少突胶质细胞谱系进展伴随着许多转录本上 m6A 修饰的动态变化。尽管少突胶质细胞前体细胞 (OPC) 数量正常,但重要 m6A 编写器组件 METTL14 的体内条件失活会导致少突胶质细胞数量减少和 CNS 髓鞘形成不足。体外 Mettl14 消融会破坏有丝分裂后少突胶质细胞的成熟,并对 OPC 和少突胶质细胞转录组有不同的影响。而且,少突胶质细胞谱系细胞中 Mettl14 的缺失会导致无数 RNA 转录物的异常剪接,包括那些编码必需的偏节点成分神经成束蛋白 155 (NF155) 的转录物。总之,我们的研究结果表明动态 RNA 甲基化在少突胶质细胞发育和 CNS 髓鞘形成中起着重要的调节作用。
更新日期:2019-12-31
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