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
Yue Wang
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
Tong Zhou
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, United States
Sheng Chen
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
Dayton Morris
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, United States
Rubens Daniel Miserani Magalhães
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, United States
Musheng Li
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, United States
Shawn Wang
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, United States
Hetan Wang
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
Yeming Xie
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, United States
Hayden McSwiggin
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
Daniel Oliver
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, United States
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, United States
Huili Zheng
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
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; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (SLITRK2 and FMR1) 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 MIR-506 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 MIR-506 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 MIR-506 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 MIR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.