Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, United States.
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, United States.
Elife. 2024 Apr 19;13:RP90203. doi: 10.7554/eLife.90203.
Despite rapid evolution across eutherian mammals, the X-linked family miRNAs are located in a region flanked by two highly conserved protein-coding genes ( and ) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the family led to reduced male fertility in mice. Despite normal sperm counts, motility, and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.
尽管真兽类哺乳动物的进化速度很快，但 X 连锁家族 miRNAs 位于 X 染色体上两个高度保守的蛋白质编码基因（和）侧翼的区域。有趣的是，这些 miRNAs 主要在睾丸中表达，表明它们在精子发生和男性生育力中可能发挥作用。在这里，我们报告 X 连锁家族 miRNAs 源自 MER91C DNA 转座子。单个 miRNAs 或簇的选择性失活不会导致明显的缺陷，但同时消融包含 19 个成员的五个簇导致小鼠的雄性生育力降低。尽管精子计数、活力和形态正常，但 KO 精子在多配偶交配方案下的竞争力低于野生型精子。转录组和生物信息学分析表明，这些 X 连锁家族 miRNAs 除了靶向一组保守基因外，还有更多在进化过程中对精子发生和胚胎发育至关重要的靶标。我们的数据表明，家族 miRNAs 通过在精子发生过程中精细调节基因表达，增强精子的竞争力和雄性的生殖适应性。
