YTHDF2 is essential for spermatogenesis and fertility through mediating a wave of transcript transition during spermatogonial differentiation
biorxiv(2020)
摘要
The dynamic and reversible regulation roles of mA modification, and the characterization of mA readers have provided new insights into spermatogenesis at post-transcriptional level. YTHDF2 has been reported to recognize and mediate the mA-containing transcripts decay during the mouse oocyte mature, embryonic stem cell differentiation, neural development, and zebrafish maternal-to-zygotic transition. However, the roles of YTHDF2 in mammalian spermatogenesis are uncertain. Here, we generated germ cell-specific mutants () at a C57BL/6J background, and demonstrated that YTHDF2 was essential for mouse spermatogenesis and fertility. provided oligoasthenoteratozoospermia (OAT) phenotype with increased apoptosis in germ cells. High-throughput RNA-seq of the testis tissue showed the failure of the degradation of a wave of YTHDF2 target mRNA. Interestingly, RNA-seq analysis combined with our previous single-cell transcriptomics data of mouse spermatogenesis pointed out the failure of a wave of transcript transition during the spermatogenesis of , which was confirmed by gene expression analysis of diplotene spermatocytes and round spermatids obtained through fluorescence-activated cell sorting using qPCR. Our study demonstrates the fundamental role of YTHDF2 during mouse spermatogenesis and provides a potential candidate for the diagnosis of male infertility with OAT syndrome.
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