A Sex Chromosome piRNA Promotes Robust Dosage Compensation and Sex Determination in <i>C. elegans</i>

Abstract

In metazoans, Piwi-related Argonaute proteins engage piRNAs (Piwi-interacting small RNAs) to defend the genome against invasive nucleic acids, such as transposable elements. Yet many organisms — including worms and humans — express thousands of piRNA that do not target transposons, suggesting that piRNA function extends beyond genome defense. Here we show that the X chromosome-derived piRNA 21ux-1 downregulates XOL-1 (XO Lethal), a master regulator of X-chromosome dosage compensation and sex determination in C. elegans. Mutations in 21ux-1 and several Piwi-pathway components sensitize hermaphrodites to dosage compensation and sex determination defects. Our findings reveal a physiologically important piRNA–mRNA interaction, raising the possibility that piRNAs function broadly to ensure robust gene expression and germline development.