Organisms are constantly challenged by the surrounding environment and alter their physiology accordingly. Some environment-induced changes in one generation are inherited in the offspring, and this long-lasting memory of parental experience has gained a lot of attention recently due to its implications in the organism's development and health. One example is transmission of RNAi-induced silencing from parents to progeny in C. elegans. Although this phenomenon has been known for more than a decade, the parental contribution to RNAi inheritance is still unclear. Here, we show that the nuclear hormone receptor DAF-12 mediates a cross-generational signaling that regulates RNAi in zygotes. Pol II ChIP-qPCR revealed that normally, DAF-12 enhances transcriptional repression induced by RNAi. Mutant analysis demonstrated that the role of DAF-12 in RNAi is distinct from its function in developmental timing or heterochronic pathways. Surprisingly, DAF-12 acts in mothers to alter the RNAi efficiency in zygotes, indicating the presence of mother-to-offspring, DAF-12-dependent signals that enhance RNAi in zygotes. Considering the previous studies showing that the function of DAF-12 is determined by environmental cues, we tested and found that the role of DAF-12 in RNAi enhancement in zygotes depends on the environmental cues presented to mothers during their development. These results demonstrate a novel role of DAF-12 as a modulator of RNAi and its contribution to cross-generational signaling. Moreover, the findings imply a potential interaction between environmental conditions and small RNA pathways.
