A model for the enhancement of certain RNAi processes in rrf-3 and eri-1 mutants, based on our observations that rrf-3 and eri-1 animals exhibit defects in certain endogenous RNAi processes, including accumulation of tncRNAs (Fig. 1; Table 1) and repression of endogenous genes (Fig. 3; Table 2; see Table S1 at http://chronic.dartmouth.edu/VRA/Lee_etal_2006_Table_S1). (A) In the wild type, multiple RNAi pathways are engaged in silencing elicited by nuclear transcription (e.g., endo-RNAi and transcriptional gene silencing [TGS]) or by exogenously supplied dsRNA. All of these pathways involve certain core RNAi components (represented by the red oval) (Tabara et al. 1999; Grishok et al. 2005; Kim et al. 2005), while more specialized components (represented by triangles, square, and hexagon) are involved in distinct pathways for silencing of subsets of endogenous genes, TGS, and/or exogenous RNAi. In this model, specialized factors for exo-RNAi/TGS (triangles) are posited to be in excess. (B) In eri-1 mutants, the loss of ERI-1 protein activity disables a branch of endogenous RNAi, leading to the liberation of core components (red oval) that then supplement complementary pathways (in this case, exogenous RNAi and TGS). (C) In rrf-3 mutants, the loss of RRF-3 protein activity similarly disables another branch of endogenous RNAi, leading to the liberation of core components that then supplement complementary pathways.
