C. elegans Dicer stacks with the RIG-I-like receptor DRH-1 to cleave dsRNA

In prior studies we showed that the nematode ancestor of Dicer's helicase domain had minimal ATP hydrolysis, translocation and dsRNA binding activity, and in extant C. elegans the RIG-I like receptor (RLR) DRH-1, and the dsRNA binding protein RDE-4, were co-opted to provide these activities. Here we report cleavage-competent cryo-EM structures of the antiviral complex (AVC; DCR-1{middle dot}DRH-1{middle dot}RDE-4), in the absence (3.2[A]) and presence (3.0[A] of ATP. A key feature of both structures is stacking of DCR-1's helicase with the helicases of two DRH-1 molecules, reminiscent of oligomerization of mammalian RLRs. dsRNA threads through all three helicases with a widened major groove at helicase-helicase interfaces and where the conserved Hel2 loop inserts into the major groove. The presence of nucleotide redistributed helicase-helicase and helicase-RNA contacts in the AVC, as for MDA5, albeit specific interactions and remodeling differed. MDA5 and RIG-I RLRs contain an unstructured linker between their CARDs and helicase domain, but the analogous linker in DRH-1 has a short-structured region positioned to interact with DCR-1. These findings provide a structural framework for understanding how DCR-1, DRH-1, and RDE-4 cooperate to cleave viral dsRNA and elucidate unique features required for antiviral defense in different animals.