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

By Pei-Hsuan Wu, Yu Fu, Katharine Cecchini, Deniz M. Özata, Amena Arif, Tianxiong Yu, Cansu Colpan, Ildar Gainetdinov, Zhiping Weng, Phillip D. Zamore

Posted 07 Aug 2018
bioRxiv DOI: 10.1101/386201

Pachytene 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 by pi6 −/− fathers show reduced viability in utero. Molecular analyses suggest that pi6 piRNAs repress gene expression by cleaving mRNAs encoding proteins required for sperm function. pi6 also participates in a network of piRNA-piRNA precursor interactions that initiate piRNA production from a second piRNA locus on chromosome 10 as well as pi6 itself. Our data establish a direct role for pachytene piRNAs in spermiogenesis and embryo viability. Highlights

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