Distinct nuclear and cytoplasmic machineries cooperatively promote the inheritance of RNAi in Caenorhabditis elegans.

Epigenetic information can be inherited over multiple generations, which is termed as transgenerational epigenetic inheritance (TEI). Although the mechanism(s) of TEI remains poorly understood, noncoding RNAs have been demonstrated to play important roles in TEI. In many eukaryotes, double-stranded RNA (dsRNA) triggers the silencing of cellular nucleic acids that exhibit sequence homology to the dsRNA via a process termed RNA interference (RNAi). In Caenorhabditis elegans, dsRNA-directed gene silencing is heritable and can persist for a number of generations after its initial induction. During the process, small RNAs and the RNAi machinery mediate the initiation, transmission and re-establishment of the gene silencing state. In this review, we summarise our current understanding of the underlying mechanism(s) of transgenerational inheritance of RNAi in C. elegans and propose that multiple RNAi machineries may act cooperatively to promote TEI.