Mettl3-mediated m ^6A regulates spermatogonial differentia- tion and meiosis initiation  

作　　者：Kai Xu Ying- Yang Gui-Hai Feng Bao-Fa Sun Jun-Qing Chen Yu-Fei Li Yu-Sheng Chen Xin-Xin Zhang Chen-Xin Wang Li-Yuan Jiang Chao Liu Ze-Yu Zhang Xiu-Jie Wang Qi Zhou Yun-Gui Yang Wei Li 

机构地区：[1]State Key Laboratory of Stem Ceil and Reproductive Biology, institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2]Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, CAS Center for Excellence in Molecular Cell Science, Beijing Institute of Genomics, Chinese Aeademy of Sciences, Beijing 100101, China [3]State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, China [4]Key Laboratory of Genetic Network Biology, Collaborative Innovation Center of Genetics and Development, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China [5]University of Chinese Academy of Sciences, Beijing 100049, China

出　　处：《Cell Research》2017年第9期1100-1114,共15页细胞研究（英文版）

基　　金：We thank Dr Y-L Zhao from Beijing Institute of Genomics,Chinese Academy of Sciences for scientific suggestion. This work was supported by the National Natural Science Foundation of China （31422038, 31471395, 31625016 and 31670824）, the National Basic Research Program of China （2014CB964800, 2016YFC0900300）, CAS Strategic Priority Research Program （XDB14030300, QYZDY-SSW-SMC027/002, QYZDB-SSW- SMC022）. We thank BIG sequencing core facility for sequencing.

摘　　要：METTL3 catalyzes the formation of N%methyl-adenosine （m6A） which has important roles in regulating various biological processes. However, the in vivo function of Mettl3 remains largely unknown in mammals. Here we gener- ated germ cell-specific Mettl3 knockout mice and demonstrated that Mettl3 was essential for male fertility and sper- matogenesis. The ablation of Mettl3 in germ cells severely inhibited spermatogonial differentiation and blocked the initiation of meiosis. Transcriptome and m6A 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 MettD-mediated m6A modification in spermatogenesis and reproduction in mammals.

关 键 词：Mettt3 m6A SPERMATOGENESIS spermatogonial differentiation MEIOSIS alternative splicing 

分 类 号：Q253[生物学—细胞生物学] S966.4[农业科学—水产养殖]