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Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis
Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis
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Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis
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Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis
Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis

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Mettl3-/Mettl14-mediated mRNA N 6 -methyladenosine modulates murine spermatogenesis
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.