
The C. elegans antiviral complex comprising Dicer (DCR-1), the RIG-I-like helicase DRH-1, and the dsRNA binding protein RDE-4 cooperate to cleave viral dsRNA in an ATP-dependent and terminus-specific manner, with DRH-1 playing a dominant role in ATP hydrolysis and processive cleavage.


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Invertebrates use the endoribonuclease Dicer to cleave viral dsRNA during antiviral defense, while vertebrates use RIG-I-like Receptors (RLRs), which bind viral dsRNA to trigger an interferon response. While some invertebrate Dicers act alone during antiviral defense, C. elegans Dicer acts in a complex with a dsRNA binding protein called RDE-4, and an RLR ortholog called DRH-1. We used biochemical and structural techniques to provide mechanistic insight into how these proteins function together. We found RDE-4 is important for ATP-independent and ATP-dependent cleavage reactions, while helicase domains of both DCR-1 and DRH-1 contribute to ATP-dependent cleavage. DRH-1 plays the dominant role in ATP hydrolysis, and like mammalian RLRs, has an N-terminal domain that functions in autoinhibition. A cryo-EM structure indicates DRH-1 interacts with DCR-1’s helicase domain, suggesting this interaction relieves autoinhibition. Our study unravels the mechanistic basis of the collaboration between two helicases from typically distinct innate immune defense pathways.

### Competing Interest Statement

The authors have declared no competing interest.

C. elegans Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA

mechanistic-insights-into-the-collaboration-of-dicer-rig-i-like-helicase-and-dsrna-binding-protein-in-antiviral-defense-in-c-elegans


Mechanistic Insights into the Collaboration of Dicer, RIG-I-like Helicase, and dsRNA Binding Protein in Antiviral Defense in C. elegans
