Mettl3-/Mettl14-mediated MRNA N-methyladenosine Modulates Murine Spermatogenesis

Overview

Journal Cell Res

Specialty Cell Biology

Date 2017 Sep 16

PMID 28914256

Citations 217

Authors

Zhen Lin

Phillip J Hsu

Xudong Xing

Jianhuo Fang

Zhike Lu

Qin Zou

Ke-Jia Zhang

Xiao Zhang

Yuchuan Zhou

Teng Zhang

Youcheng Zhang

Wanlu Song

Guifang Jia

Xuerui Yang

Chuan He

Ming-Han Tong

Affiliations

Soon will be listed here.

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 N-methyladenosine (mA), an epitranscriptomic mark regulating gene expression, plays essential roles during spermatogenesis. We present comprehensive mA 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 mA RNA methyltransferase Mettl3 or Mettl14 with Vasa-Cre causes loss of mA and depletion of SSCs. mA 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 mA modification in germline development, potentially ensuring coordinated translation at different stages of spermatogenesis.

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