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通过m6A甲基化对哺乳动物皮层神经发生的时间控制

Ki-Jun Yoon¹, Francisca Rojas Ringeling², Caroline Vissers³

¹Department of Neuroscience and Mahoney Institute for Neurosciences, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

|October 3, 2017

概括

对于哺乳动物的大脑发育而言,N6-甲基氨酸 (m6A) 的RNA修饰至关重要. 在小鼠中减少m6A扩展了神经发生,并揭示了它在皮层发育过程中协调基因表达的作用.

科学领域:

神经科学
表观遗传学
分子生物学

背景情况:

N6-甲基氨酸 (m6A) 是最丰富的内部mRNA修饰.
m6A在哺乳动物大脑发育中的作用在很大程度上仍未被探索.

研究的目的:

研究m6A在哺乳动物皮层发育中的作用.
阐明调节神经发生的表体转录机制.

主要方法:

在胚胎小鼠大脑中通过Mettl14淘汰和Mettl3淘汰减少m6A.
胚胎小鼠皮层的m6A测序 (m6A-seq).
对人类前脑器官进行分析.

主要成果:

m6A消耗延长了辐射质细胞周期和扩展皮质神经发生.
m6A测序发现了特定的mRNA类别的丰富,m6A标记促进了衰变.
m6A信号调节人类皮质神经发生,并显示脑疾病风险基因中的人类特异性模式.

结论:

m6A信号传递是哺乳动物皮层神经发生的关键调节者.
这项研究揭示了在大脑发育过程中协调转录的表体转录机制.
这些发现突显了m6A在与大脑疾病相关的人类特异性基因调节中的作用.

关键词:

没有.甲基化RNA 自闭症表体转录组学人类器官 m(6) 一个神经发生放射性质细胞精神分裂症转录预模式

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Epigenetic Regulation

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Epigenetic Regulation

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