A Matter of Time: Small RNAs Regulate the Duration of Epigenetic Inheritance

Small RNAs are increasingly emerging as transgenerational carriers of epigenetic information in Caenorhabditis elegans and in other organisms. Recent studies have identified factors that are required for the inheritance of small RNAs and for heritable RNAi in worms, which typically persist for a finite number of generations. We examine here recent insights into the mechanisms that control the duration of transgenerational inheritance of small RNAs. We discuss current understanding of two types of regulatory mechanisms: those that prolong RNAi inheritance through amplification and maintenance of heritable small RNAs, and those that limit the persistence of ancestral RNAi by, for example, employing negative feedback loops to reset the transmission of epigenetic information. Collectively, these machineries result in the precise and intricate regulation of small RNA inheritance across generations.