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

• DOI: 10.7554/elife.93979.2
• Publication Date: 2024-04-03T13:20:52Z
• Authors: Claudia D. Consalvo; Adedeji M. Aderounmu; Helen M. Donelick; P. Joe Aruscavage; Debra M. Eckert; Peter S. Shen; Brenda L. Bass
• Keywords: RNA Helicase A; Dicer; RNA Silencing; Endoribonuclease; MDA5; Ribonuclease III

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