Mettl3-/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis

查看全文 作　　者：Zhen [1]Lin;Phillip J [2]Hsu;Xudong [3]Xing;Jianhuo [3]Fang;Zhike [2]Lu;Qin [3]Zou;Ke-Jia [1]Zhang;Xiao [4]Zhang;Yuchuan [1]Zhou;Teng [1]Zhang;Youcheng [1]Zhang;Wanlu [3]Song;Guifang [4]Jia;Xuerui [3]Yang;Chuan [2,4]He;Ming-Han [1]Tong

机构地区：[1]State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China;[2]Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chica- go, IL 60637, USA;[3]MOE Key Laboratory of Bioinformatics, Center for Synthetic & Systems Biology, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;[4]Synthetic and Functional Biomolecules Center, Beo'ing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Min- istry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

出　　处：《Cell Research》索引2017年第27卷第10期,共15页

基　　金：M-HT was supported by the Strategic Priority Research Pro- gram of the Chinese Academy of Sciences (XDB19000000), the Ministry of Science and Technology of China (2014CB943101), the National Key Research and Development Program of China (2016YFC1000600), SIBS foundation, the National Natural Science Foundation of China (31471401 and 31671553), the Science and Technology Commission of Shanghai Municipality (14140901502 and 14JC1407100). This work was also supported by NIH HG008688 (CH). CH is an investigator of the Howard Hughes Medical Institute. XY was supported by the National Natural Science Foundation of China (81472855 and 91540109), the Ministry of Science and Technology of China Grant (2016YFC0906001). We thank the Histology, Flow Cytometry and Vivarium services at SIBCB, and the Genome Sequencing and High-performance Computing services from the National Protein Science Facility (Beijing) at Tsinghua University. 摘　　要：精子发生在双 spermatogonial 干细胞(SSC ) 哪个生产 haploid 精子期间是一个区别过程。这个高度专业化的过程精确在 transcriptional, posttranscriptional,和翻译层次被控制。这里,我们报导那 N ⁶-methyladenosine (m ⁶ 一) ,调整基因表示的一个 epitranscriptomic 标记,在精子发生期间起必要作用。我们现在的全面 m ⁶ 从五个发展阶段的老鼠 spermatogenic 房间的 mRNA methylomes:无差别的 spermatogonia,类型 A ₁ spermatogonia, preleptotene spermatocytes, pachytene/diplotene spermatocytes,和圆 spermatids。m ⁶ 有 Vasa-Cre 的 RNA methyltransferase Mettl3 或 Mettl14 引起 m ⁶ SSC 的 A 和弄空。m ⁶ 为 SSC 增长 / 区别被要求的抄本的一个弄空 dysregulates 翻译。在有 Stra8-GFPCre 的先进细菌房间的 Mettl3 和 Mettl14 的联合删除破坏精子形式,而有在先进细菌房间的 Mettl3 或 Mettl14 的单个删除的老鼠显示出正常精子发生。从双异种老鼠展览的 spermatids 损害了为精子形式是必要的 haploid 特定的基因的翻译。这研究加亮 mRNA m ⁶ 在 germline 开发的修正,潜在地保证在精子发生的不同阶段协调了翻译。 关键词：MRNA 精子发生过程分化过程基因表达调控生殖细胞突变小鼠 SSCS 精原细胞

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Mettl3-/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis

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