Mettl3 介导的 mA 调节精原细胞分化和减数分裂起始。
Mettl3-mediated mA regulates spermatogonial differentiation and meiosis initiation.
机构信息
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
出版信息
Cell Res. 2017 Sep;27(9):1100-1114. doi: 10.1038/cr.2017.100. Epub 2017 Aug 15.
Abstract
METTL3 catalyzes the formation of N-methyl-adenosine (mA) which has important roles in regulating various biological processes. However, the in vivo function of Mettl3 remains largely unknown in mammals. Here we generated germ cell-specific Mettl3 knockout mice and demonstrated that Mettl3 was essential for male fertility and spermatogenesis. The ablation of Mettl3 in germ cells severely inhibited spermatogonial differentiation and blocked the initiation of meiosis. Transcriptome and mA profiling analysis revealed that genes functioning in spermatogenesis had altered profiles of expression and alternative splicing. Our findings provide novel insights into the function and regulatory mechanisms of Mettl3-mediated mA modification in spermatogenesis and reproduction in mammals.
摘要
METTL3 催化 N6-甲基腺苷（m6A）的形成，m6A 在调节各种生物过程中具有重要作用。然而，Mettl3 在哺乳动物体内的功能在很大程度上尚不清楚。在这里，我们生成了生殖细胞特异性的 Mettl3 敲除小鼠，并证实 Mettl3 对于雄性生育力和精子发生是必需的。生殖细胞中 Mettl3 的缺失严重抑制了精原细胞的分化，并阻断了减数分裂的起始。转录组和 m6A 谱分析显示，在精子发生中起作用的基因的表达和选择性剪接发生了改变。我们的研究结果为 Mettl3 介导的 m6A 修饰在哺乳动物精子发生和生殖中的功能和调控机制提供了新的见解。
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本文引用的文献
1
The mA pathway facilitates sex determination in Drosophila.mA 通路促进果蝇的性别决定。
Nat Commun. 2017 Jul 4;8:15737. doi: 10.1038/ncomms15737.
2
mA mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover.mA信使核糖核酸修饰存在于新生的前体信使核糖核酸中，剪接过程并不需要这些修饰，但它们确实决定了细胞质中的周转情况。
Genes Dev. 2017 May 15;31(10):990-1006. doi: 10.1101/gad.301036.117.
3
Kaposi's Sarcoma-Associated Herpesvirus Utilizes and Manipulates RNA N-Adenosine Methylation To Promote Lytic Replication.卡波西肉瘤相关疱疹病毒利用并操纵RNA N-腺苷甲基化以促进裂解复制。
J Virol. 2017 Jul 27;91(16). doi: 10.1128/JVI.00466-17. Print 2017 Aug 15.
4
Single-Cell RNA-Seq Analysis Maps Development of Human Germline Cells and Gonadal Niche Interactions.单细胞RNA测序分析描绘人类生殖细胞发育及性腺微环境相互作用图谱。
Cell Stem Cell. 2017 Jun 1;20(6):891-892. doi: 10.1016/j.stem.2017.05.009.
5
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Mol Cell Biol. 2017 Jun 29;37(14). doi: 10.1128/MCB.00632-16. Print 2017 Jul 15.
6
N6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein.N6-甲基腺苷改变RNA结构以调节低复杂性蛋白质的结合。
Nucleic Acids Res. 2017 Jun 2;45(10):6051-6063. doi: 10.1093/nar/gkx141.
7
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8
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Nature. 2017 Feb 23;542(7642):475-478. doi: 10.1038/nature21355. Epub 2017 Feb 13.
9
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Nat Commun. 2017 Jan 27;8:14182. doi: 10.1038/ncomms14182.
10
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