Principles of Transgenerational Small RNA Inheritance in Caenorhabditis elegans

Examples of transgenerational inheritance of environmental responses are rapidly accumulating. In Caenorhabditis elegans nematodes, such heritable information transmits across generations in the form of RNA-dependent RNA polymerase-amplified small RNAs. Regulatory small RNAs enable sequence-specific gene regulation, and unlike chromatin modifications, can move between tissues, and escape from immediate germline reprogramming. In this review, we discuss the path that small RNAs take from the soma to the germline, and elaborate on the mechanisms that maintain or erase parental small RNA responses after a specific number of generations. We focus on the intricate interactions between heritable small RNAs and histone modifications, deposited on specific loci. A trace of heritable chromatin marks, in particular trimethylation of histone H3 lysine 9, is deposited on RNAi-targeted loci. However, how these modifications regulate RNAi or small RNA inheritance was until recently unclear. Integrating the very latest literature, we suggest that changes to histone marks may instigate transgenerational gene regulation indirectly, by affecting the biogenesis of heritable small RNAs. Inheritance of small RNAs could spread adaptive ancestral responses.