An Evolutionarily Conserved piRNA-producing Locus Required for Male Mouse Fertility

Abstract

SUMMARYPachytene piRNAs, which comprise >80% of small RNAs in the adult mouse testis, have been proposed to bind and regulate target RNAs like miRNAs, cleave targets like siRNAs, or lack biological function altogether. Although piRNA pathway protein mutants are male sterile, no biological function has been identified for any mammalian piRNA-producing locus. Here, we report that males lacking piRNAs from a conserved mouse pachytene piRNA locus on chromosome 6 (pi6) produce sperm with defects in capacitation and egg fertilization. Moreover, heterozygous embryos sired bypi6−/−fathers show reduced viability in utero. Molecular analyses suggest thatpi6piRNAs repress gene expression by cleaving mRNAs encoding proteins required for sperm function.pi6also participates in a network of piRNA-piRNA precursor interactions that initiate piRNA production from a second piRNA locus on chromosome 10 as well aspi6itself. Our data establish a direct role for pachytene piRNAs in spermiogenesis and embryo viability.HighlightsNormal male mouse fertility and spermiogenesis require piRNAs from thepi6locusSperm capacitation and binding to the zona pellucida of the egg requirepi6piRNAsHeterozygous embryos sired bypi6−/−fathers show reduced viability in uteroDefects inpi6mutant sperm reflect changes in the abundance of specific mRNAs.