The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility
RNA Therapeutics Institute; Program in Bioinformatics and Integrative Biology; Department of Biochemistry and Molecular Pharmacology; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Biochemistry | Bioinformatics | Cell and Developmental Biology | Developmental Biology | Genetics and Genomics | Nucleic Acids, Nucleotides, and Nucleosides | Reproductive and Urinary Physiology | Urogenital System
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.
Functional genomics, RNAi, Spermatogenesis, Transcriptomics
DOI of Published Version
Wu PH, Fu Y, Cecchini K, Özata DM, Arif A, Yu T, Colpan C, Gainetdinov I, Weng Z, Zamore PD. The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility. Nat Genet. 2020 Jul;52(7):728-739. doi: 10.1038/s41588-020-0657-7. Epub 2020 Jun 29. PMID: 32601478; PMCID: PMC7383350. Link to article on publisher's site
P, Fu Y, Cecchini K, Ozata DM, Arif A, Yu T, Colpan C, I, Weng Z, Zamore PD. (2020). The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1038/s41588-020-0657-7. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1731