ArticleeLife2023
Ancestral protein reconstruction reveals evolutionary events governing variation in Dicer helicase function.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Dicer Deletion in the Ear Can Cut Most Neurons and Their Innervation of Hair Cells to Project to the Ear and the Brainstem.International journal of molecular sciences · 2026Article
- The chromosome-level genome assembly of the slug Deroceras laeve facilitates its use as a comparative model of regeneration.G3 (Bethesda, Md.) · 2025Article
- Lineage-specific expansions of the Dicer gene family in tardigrades.BMC genomics · 2025Article
- Response to "Antiviral RNA silencing in mammals: the importance of selecting the appropriate experimental model".Nucleic acids research · 2025Article
- Biochemical and structural basis of Dicer helicase function unveiled by resurrecting ancient proteins.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Enhanced RNAi does not provide efficient innate antiviral immunity in mice.Nucleic acids research · 2025Article
- The human Dicer helicase domain is capable of ATP hydrolysis and single-stranded nucleic acid binding.BMC biology · 2024Article
- Article
- Double-stranded RNA induces antiviral transcriptional response through the Dicer-2/Ampk/FoxO axis in an arthropod.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Functional canonical RNAi in mice expressing a truncated Dicer isoform and long dsRNA.EMBO reports · 2024Article
- Article
- The Evolution and Characterization of the RNA Interference Pathways in Lophotrochozoa.Genome biology and evolution · 2024Article
- Article
- Article
- Structural mechanism of R2D2 and Loqs-PD synergistic modulation on DmDcr-2 oligomers.Nature communications · 2023Article
- Dicer structure and function: conserved and evolving features.EMBO reports · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
Antiviral defense in ecdysozoan invertebrates requires Dicer with a helicase domain capable of ATP hydrolysis. But despite well-conserved ATPase motifs, human Dicer is incapable of ATP hydrolysis, consistent with a muted role in antiviral defense. To investigate this enigma, we used ancestral protein reconstruction to resurrect Dicer's helicase in animals and trace the evolutionary trajectory of ATP hydrolysis. Biochemical assays indicated ancient Dicer possessed ATPase function, that like extant invertebrate Dicers, is stimulated by dsRNA. Analyses revealed that dsRNA stimulates ATPase activity by increasing ATP affinity, reflected in Michaelis constants. Deuterostome Dicer-1 ancestor, while exhibiting lower dsRNA affinity, retained some ATPase activity; importantly, ATPase activity was undetectable in the vertebrate Dicer-1 ancestor, which had even lower dsRNA affinity. Reverting residues in the ATP hydrolysis pocket was insufficient to rescue hydrolysis, but additional substitutions distant from the pocket rescued vertebrate Dicer-1's ATPase function. Our work suggests Dicer lost ATPase function in the vertebrate ancestor due to loss of ATP affinity, involving motifs distant from the active site, important for coupling dsRNA binding to the active conformation. By competing with Dicer for viral dsRNA, RIG-I-like receptors important for interferon signaling may have allowed or actively caused loss of ATPase function.
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