Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi

The type III ribonuclease DCR-1 is essential for ERI endogenous RNAi and exogenous RNAi in Caenorhabditis elegans . A new study shows that DCR-1 forms exclusive complexes in each pathway, and characterization of the ERI complex implicates a tudor domain protein in tethering an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi. Endogenous RNA interference (endo-RNAi) pathways use a variety of mechanisms to generate siRNA and to mediate gene silencing. In Caenorhabditis elegans , DCR-1 is essential for competing RNAi pathways—the ERI endo-RNAi pathway and the exogenous RNAi pathway—to function. Here, we demonstrate that DCR-1 forms exclusive complexes in each pathway and further define the ERI–DCR-1 complex. We show that the tandem tudor protein ERI-5 potentiates ERI endo-RNAi by tethering an RNA-dependent RNA polymerase (RdRP) module to DCR-1. In the absence of ERI-5, the RdRP module is uncoupled from DCR-1. Notably, EKL-1, an ERI-5 paralog that specifies distinct RdRP modules in Dicer-independent endo-RNAi pathways, partially compensates for the loss of ERI-5 without interacting with DCR-1. Our results implicate tudor proteins in the recruitment of RdRP complexes to specific steps within DCR-1-dependent and DCR-1-independent endo-RNAi pathways.