Wang Zhuqing, Wang Yue, Zhou Tong, Chen Sheng, Morris Dayton, Magalhães Rubens Daniel Miserani, Li Musheng, Wang Shawn, Wang Hetan, Xie Yeming, McSwiggin Hayden, Oliver Daniel, Yuan Shuiqiao, Zheng Huili, Mohammed Jaaved, Lai Eric C, McCarrey John R, Yan Wei
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA.
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
bioRxiv. 2024 Jan 20:2023.06.14.544876. doi: 10.1101/2023.06.14.544876.
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 discernable defects, but simultaneous ablation of five clusters containing nineteen 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.
尽管真兽亚纲哺乳动物中存在快速进化，但X连锁的 家族微小RNA（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雄性生育力中可能发挥作用。在这里，我们报告X连锁的 家族miRNAs来源于MER91C DNA转座子。单个miRNAs或簇的选择性失活未导致明显缺陷，但同时敲除包含 家族19个成员的5个簇会导致小鼠雄性生育力下降。尽管精子数量、活力和形态正常，但在多雄交配方案中，基因敲除（KO）精子的竞争力低于野生型精子。转录组学和生物信息学分析表明，这些X连锁的 家族miRNAs除了靶向一组保守基因外，还有更多对精子发生和进化过程中的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微调基因表达来增强雄性精子的竞争力和生殖适应性。
