Figure 5.

Genetic requirements for primary and secondary siRNA generation. (A) Model for RNAi in C. elegans. Exogenous dsRNA is processed by DCR-1 and RDE-4 into primary siRNAs. Short dsRNAs are then delivered to RDE-1, potentially through an additional role of the dsRNA binding factor. RDE-1 then cleaves the passenger strand, allowing subsequent maturation into active RISC. The RDE-1 RISC then recruits the RdRP (RRF-1 or EGO-1) to the target RNA where the latter engages in secondary siRNA synthesis using the target as template. Primary siRNA-complexed RDE-1 may endonucleolytically destroy targ et RNAs, while secondary siRNAs complex with the WAGOs and presumably further downregulate the target RNA via an unknown mechanism. (B) Mutations in RNAi factors affect primary and/or secondary siRNA synthesis. Pie charts indicate fraction of antisense sel-1 siRNAs comprised by trigger-matched (red), target-matched (blue), and ambiguous (black) antisense sel-1 siRNAs. Numbers below pie charts indicate percentage of total small RNAs (sRNAs) comprised of sel-1 siRNAs. (See also Figure S4.)