| Literature DB >> 28914256 |
Zhen Lin1, Phillip J Hsu2, Xudong Xing3, Jianhuo Fang3, Zhike Lu2, Qin Zou3, Ke-Jia Zhang1, Xiao Zhang4, Yuchuan Zhou1, Teng Zhang1, Youcheng Zhang1, Wanlu Song3, Guifang Jia4, Xuerui Yang3, Chuan He2,4, Ming-Han Tong1.
Abstract
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 N6-methyladenosine (m6A), an epitranscriptomic mark regulating gene expression, plays essential roles during spermatogenesis. We present comprehensive m6A mRNA methylomes of mouse spermatogenic cells from five developmental stages: undifferentiated spermatogonia, type A1 spermatogonia, preleptotene spermatocytes, pachytene/diplotene spermatocytes, and round spermatids. Germ cell-specific inactivation of the m6A RNA methyltransferase Mettl3 or Mettl14 with Vasa-Cre causes loss of m6A and depletion of SSCs. m6A 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 m6A modification in germline development, potentially ensuring coordinated translation at different stages of spermatogenesis.Entities:
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Year: 2017 PMID： 28914256 PMCID： PMC5630681 DOI： 10.1038/cr.2017.117
Source DB: PubMed Journal: Cell Res ISSN： 1001-0602 Impact factor: 25.617