PT  - JOURNAL ARTICLE
AU  - Pei-Hsuan Wu
AU  - Yu Fu
AU  - Katharine Cecchini
AU  - Deniz M. Özata
AU  - Zhiping Weng
AU  - Phillip D. Zamore
TI  - An Evolutionarily Conserved piRNA-producing Locus Required for Male Mouse Fertility
AID  - 10.1101/386201
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 386201
4099  - http://biorxiv.org/content/early/2018/08/07/386201.short
4100  - http://biorxiv.org/content/early/2018/08/07/386201.full
AB  - SUMMARY Pachytene piRNAs, which comprise >80% of all small RNAs in the adult mouse testis, have been proposed to bind and regulate target RNAs like miRNAs, to cleave targets like siRNAs, or to lack biological function altogether. Although mutants lacking proteins that make pachytene piRNAs are male sterile, no biological function has been identified for any mammalian piRNA-producing locus. Here, we report that loss of piRNA precursor transcription from a conserved pachytene piRNA locus on mouse chromosome 6 (pi6) perturbs male fertility. Loss of pi6 piRNAs has no measurable effect on sperm quantity or transposon repression, yet pi6−/− mice produce sperm with defects in motility, egg fertilization, and embryo development, severely reducing pup production even at the peak of male reproduction. Our data establish a direct role for pachytene piRNAs in spermiogenesis and embryo viability and enable new strategies to identify the RNA targets of individual piRNA species.HighlightsNormal male mouse fertility and spermiogenesis require piRNAs from the pi6 locusNormal sperm motility and binding to zona pellucida require pi6 piRNAsSperm from pi6 males fail to support embryo developmentDefects in pi6 sperm reflect changes in the abundance of specific mRNAs