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Cited by 12interferon and immune responsesInvertebrate Immune Response MechanismsRNA Interference and Gene Delivery

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Caenorhabditis 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 Joseph, Eckert, Debra M, Shen, Peter S, Bass, Brenda L·2024·eLife
DOI 10.7554/elife.93979.3

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Abstract

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, Caenorhabditis 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
2024-05-15
Volume
13
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.93979.3
OpenAlex
W4396924679
Cited by
12
References
1
Citations by year
2026: 5 · 2025: 3 · 2024: 4
FWCI
2.01
Type
journal article
Language
en
Open access
Licence
Locations
eLife (publishedVersion, 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
Caenorhabditis elegans, Dicer, RIG-I-like helicases, double-stranded RNA cleavage, antiviral innate immunity, ATP hydrolysis, autoinhibition, helicase domain, cryo-EM structure, protein complex structure

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CoChat. (2026). Citation check: Caenorhabditis elegans Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA. https://app.cochat.ai/papers/10.7554/elife.93979.3
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Consalvo, C. D., Aderounmu, A. M., Donelick, H. M., Aruscavage, P. J., Eckert, D. M., Shen, P. S., & Bass, B. L. (2024). Caenorhabditis elegans Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA. eLife. https://doi.org/10.7554/elife.93979.3

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