The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility

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

Research output: Contribution to journalArticlepeer-review


Pachytene PIWI-interacting RNAs (piRNAs), which comprise >80% of small RNAs in the adult mouse testis, have been proposed to bind and regulate target RNAs like microRNAs, cleave targets like short interfering RNAs 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 messenger RNAs 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.

Original languageEnglish (US)
Pages (from-to)728-739
Number of pages12
JournalNature Genetics
Issue number7
StatePublished - Jul 1 2020

ASJC Scopus subject areas

  • Genetics


Dive into the research topics of 'The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility'. Together they form a unique fingerprint.

Cite this