皮层和视网膜神经发生的 mA 调节由冗余的 mA 阅读器 YTHDFs 介导。
mA regulation of cortical and retinal neurogenesis is mediated by the redundant mA readers YTHDFs.
作者信息
Niu Fugui, Che Pengfei, Yang Zhuoxuan, Zhang Jian, Yang Lixin, Zhuang Mengru, Ou Xijun, Ji Sheng-Jian
机构信息
Harbin Institute of Technology, Harbin, Heilongjiang 150001, China.
School of Life Sciences, Department of Biology, Brain Research Center, Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
出版信息
iScience. 2022 Aug 11;25(9):104908. doi: 10.1016/j.isci.2022.104908. eCollection 2022 Sep 16.
mA modification plays an important role in regulating mammalian neurogenesis. However, whether and how the major cytoplasmic mA readers, YTHDF1, YTHDF2, and YTHDF3 mediate this process is still not clear. Here, we demonstrate that and double deletion but not individual knockout recapitulates the phenotype of knockout in cortex. In addition, we find that knockout in retina causes protracted proliferation of retinal progenitors, decreased numbers of retinal neurons, and disturbed laminar structure. This phenotype is only reproduced when , , and are knocked out simultaneously in retina. Analysis of YTHDF target mRNAs in mouse cortex and retina reveals abundant overlapping mRNAs related to neurogenesis that are recognized and regulated by both YTHDF1 and YTHDF2. Together our results demonstrate that the functionally redundant YTHDFs mediate mA regulation of cortical and retinal neurogenesis.
N6-甲基腺苷（m6A）修饰在调节哺乳动物神经发生中起重要作用。然而，主要的细胞质m6A阅读蛋白YTHDF1、YTHDF2和YTHDF3是否以及如何介导这一过程仍不清楚。在这里，我们证明YTHDF1和YTHDF2双敲除而非单个敲除可重现皮层中YTHDF1敲除的表型。此外，我们发现视网膜中YTHDF2敲除会导致视网膜祖细胞的长期增殖、视网膜神经元数量减少以及层状结构紊乱。只有当YTHDF1、YTHDF2和YTHDF3在视网膜中同时敲除时，才会重现这种表型。对小鼠皮层和视网膜中YTHDF靶mRNA的分析揭示了大量与神经发生相关的重叠mRNA，这些mRNA被YTHDF1和YTHDF2识别并调节。我们的结果共同表明，功能冗余的YTHDFs介导了皮层和视网膜神经发生的m6A调节。
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