Updated publication reference for PubMed record(s): 32015436.
Updated publication reference for PubMed record(s): 32015436, 34108460.
PIWI-interacting RNAs (piRNAs) promote fertility in many animals. Yet, whether this is due to their conserved role in repressing repetitive elements (REs) or other functions remains unclear. Here, we show that the progressive loss of fertility in Caenorhabditis elegans lacking piRNAs is not caused by derepression of REs or other piRNA targets, but rather mediated by the epigenetic silencing of all the replicative histone genes. In the absence of piRNAs, downstream components of the piRNA pathway relocalize from germ granules and piRNA targets to histone mRNAs to synthesize antisense small RNAs (sRNAs) and induce transgenerational silencing. Removal of the downstream components of the piRNA pathway is sufficient to restore histone mRNA expression and fertility in piRNA mutants, and the inheritance of histone sRNAs in wild-type worms adversely affects their fertility for multiple generations. We conclude that the transgenerational silencing of histone genes contributes to the progressive loss of fertility in piRNA mutants and that coupling piRNAs and histone silencing may serve to maintain piRNAs production across evolution.