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Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis
by
Lin, Zhen
, Zou, Qin
, Xing, Xudong
, Jia, Guifang
, Hsu, Phillip J
, Zhang, Teng
, Song, Wanlu
, He, Chuan
, Zhang, Youcheng
, Zhou, Yuchuan
, Fang, Jianhuo
, Zhang, Xiao
, Lu, Zhike
, Yang, Xuerui
, Zhang, Ke-Jia
, Tong, Ming-Han
in
Adaptor Proteins, Signal Transducing - genetics
/ Adenosine - analogs & derivatives
/ Adenosine - genetics
/ Animals
/ Cell Differentiation - genetics
/ Cell Proliferation - genetics
/ Gene Expression Regulation, Developmental - genetics
/ Male
/ Methyltransferases - genetics
/ Mice
/ RNA, Messenger - genetics
/ Spermatids - growth & development
/ Spermatids - metabolism
/ Spermatocytes - growth & development
/ Spermatocytes - metabolism
/ Spermatogenesis - genetics
/ Spermatozoa - growth & development
/ Spermatozoa - metabolism
/ Stem Cells - metabolism
/ Testis - growth & development
/ Testis - metabolism
2017
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Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis
by
Lin, Zhen
, Zou, Qin
, Xing, Xudong
, Jia, Guifang
, Hsu, Phillip J
, Zhang, Teng
, Song, Wanlu
, He, Chuan
, Zhang, Youcheng
, Zhou, Yuchuan
, Fang, Jianhuo
, Zhang, Xiao
, Lu, Zhike
, Yang, Xuerui
, Zhang, Ke-Jia
, Tong, Ming-Han
in
Adaptor Proteins, Signal Transducing - genetics
/ Adenosine - analogs & derivatives
/ Adenosine - genetics
/ Animals
/ Cell Differentiation - genetics
/ Cell Proliferation - genetics
/ Gene Expression Regulation, Developmental - genetics
/ Male
/ Methyltransferases - genetics
/ Mice
/ RNA, Messenger - genetics
/ Spermatids - growth & development
/ Spermatids - metabolism
/ Spermatocytes - growth & development
/ Spermatocytes - metabolism
/ Spermatogenesis - genetics
/ Spermatozoa - growth & development
/ Spermatozoa - metabolism
/ Stem Cells - metabolism
/ Testis - growth & development
/ Testis - metabolism
2017
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Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis
by
Lin, Zhen
, Zou, Qin
, Xing, Xudong
, Jia, Guifang
, Hsu, Phillip J
, Zhang, Teng
, Song, Wanlu
, He, Chuan
, Zhang, Youcheng
, Zhou, Yuchuan
, Fang, Jianhuo
, Zhang, Xiao
, Lu, Zhike
, Yang, Xuerui
, Zhang, Ke-Jia
, Tong, Ming-Han
in
Adaptor Proteins, Signal Transducing - genetics
/ Adenosine - analogs & derivatives
/ Adenosine - genetics
/ Animals
/ Cell Differentiation - genetics
/ Cell Proliferation - genetics
/ Gene Expression Regulation, Developmental - genetics
/ Male
/ Methyltransferases - genetics
/ Mice
/ RNA, Messenger - genetics
/ Spermatids - growth & development
/ Spermatids - metabolism
/ Spermatocytes - growth & development
/ Spermatocytes - metabolism
/ Spermatogenesis - genetics
/ Spermatozoa - growth & development
/ Spermatozoa - metabolism
/ Stem Cells - metabolism
/ Testis - growth & development
/ Testis - metabolism
2017
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Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis
Journal Article
Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis
2017
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Overview
Spermatogenesis is a differentiation process during which diploid spermatogonial stem cells (SSCs) produce haploid spermatozoa. This highly specialized process is precisely controlled at the transcriptional, posttranscriptional, and translational levels. Here we report that N
-methyladenosine (m
A), an epitranscriptomic mark regulating gene expression, plays essential roles during spermatogenesis. We present comprehensive m
A mRNA methylomes of mouse spermatogenic cells from five developmental stages: undifferentiated spermatogonia, type A
spermatogonia, preleptotene spermatocytes, pachytene/diplotene spermatocytes, and round spermatids. Germ cell-specific inactivation of the m
A RNA methyltransferase Mettl3 or Mettl14 with Vasa-Cre causes loss of m
A and depletion of SSCs. m
A depletion dysregulates translation of transcripts that are required for SSC proliferation/differentiation. Combined deletion of Mettl3 and Mettl14 in advanced germ cells with Stra8-GFPCre disrupts spermiogenesis, whereas mice with single deletion of either Mettl3 or Mettl14 in advanced germ cells show normal spermatogenesis. The spermatids from double-mutant mice exhibit impaired translation of haploid-specific genes that are essential for spermiogenesis. This study highlights crucial roles of mRNA m
A modification in germline development, potentially ensuring coordinated translation at different stages of spermatogenesis.
Subject
Adaptor Proteins, Signal Transducing - genetics
/ Adenosine - analogs & derivatives
/ Animals
/ Cell Differentiation - genetics
/ Cell Proliferation - genetics
/ Gene Expression Regulation, Developmental - genetics
/ Male
/ Methyltransferases - genetics
/ Mice
/ Spermatids - growth & development
/ Spermatocytes - growth & development
/ Spermatozoa - growth & development
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