Germ granules are biomolecular condensates that promote germ cell totipotency in animals. In C.elegans, MEG-3 and MEG-4 function redundantly to assemble germ granules in germline blastomeres. Here, we show that
meg-3/4 mutant animals exhibit defects in RNA interference (RNAi) that are transgenerationally disconnected from the
meg-3/4 genotype. Similar non-Mendelian inheritance is associated with other mutations disrupting germ granule formation, indicating that loss of germ granules is the likely cause of the observed disconnects between genotype and phenotype.
meg-3/4 animals produce aberrant siRNAs that are propagated
for10 generations in wild-type descendants of
meg-3/4 ancestors. Aberrant siRNAs inappropriately and heritably silence germline-expressed genes including the RNAi gene
sid-1, suggesting that transgenerational silencing of
sid-1 underlies inherited defects in RNAi. We conclude that one function of germ granules is to organize RNA-based epigenetic inheritance pathways and that germ granule loss has consequences that persist for many generations.