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PreprintCited by 2interferon and immune responsesInvertebrate Immune Response MechanismsRNA Interference and Gene Delivery

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

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Consalvo, Claudia D., Aderounmu, Adedeji M., Donelick, Helen M., Aruscavage, P. Joe, Eckert, Debra M., Shen, Peter S., Bass, Brenda L.·2024·eLife
DOI 10.7554/elife.93979.2

Preprint — published as 10.7554/elife.93979.3 · Paper page

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Abstract

Abstract/Summary 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.

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Metadata

Authors
Consalvo, C. D., Aderounmu, A. M., Donelick, H. M., Aruscavage, P. J., Eckert, D. M., Shen, P. S., & Bass, B. L.
Affiliations
University of Utah (US)
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2024-04-03
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.93979.2
OpenAlex
W4393910648
Cited by
2
References
1
Citations by year
2026: 1 · 2025: 1
Type
posted content
Language
en
Open access
Licence
Locations
eLife (acceptedVersion, cc-by)
Funders
  • National Institute of General Medical Sciences (R35GM141262, R35GM133772)
  • National Cancer Institute (R01CA260414)
  • National Institutes of Health (T32AI055434)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
Dicer, RIG-I-like helicases, double-stranded RNA cleavage, antiviral innate immunity, Caenorhabditis elegans, ATP hydrolysis, autoinhibition, cryo-EM structure, dsRNA-binding proteins

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