AI Article Synopsis
- Spermatogenesis involves the transformation of diploid stem cells into haploid sperm and is tightly regulated at multiple levels of gene expression.
- N-methyladenosine (mA) is identified as a significant epitranscriptomic marker that influences spermatogenesis by regulating gene expression and translational processes.
- Deleting mA-related genes in germ cells disrupts spermatogenesis and translation of crucial genes, underlining the importance of mA in normal sperm development.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630681 | PMC |
| http://dx.doi.org/10.1038/cr.2017.117 | DOI Listing |
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