ArticleMolecular cell2024
The guide-RNA sequence dictates the slicing kinetics and conformational dynamics of the Argonaute silencing complex.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Understanding the biological limits of hybridization-dependent siRNA off-target interactions.Molecular therapy. Nucleic acids · 2026Article
- License to slice: duplex deformation gates Argonaute catalysis.Nature structural & molecular biology · 2026Article
- Catalytic activation of human Argonaute 2 requires RNA duplex deformation.Nature structural & molecular biology · 2026Article
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- Divalent siRNA for prion disease.Nucleic acids research · 2026Article
- Structural dynamics between Argonaute-2 and CK1α promote target RNA release in microRNA-mediated silencing.bioRxiv : the preprint server for biology · 2026Article
- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
- The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation.bioRxiv : the preprint server for biology · 2026Article
- Detection of MicroRNAs Released from Argonautes.Methods in molecular biology (Clifton, N.J.) · 2026Article
- A unifying model for microRNA-guided silencing of messenger RNAs.Nature communications · 2025Article
- miRNA modules for precise, tunable control of gene expression.bioRxiv : the preprint server for biology · 2025Article
- Functional microRNA targeting without seed pairing.Nucleic acids research · 2025Article
- Sequence, structure, and affinity of miR-34a binding sites determine repression efficacy.Nucleic acids research · 2025Article
- Mechanistic insights into RNA cleavage by human Argonaute2-siRNA complex.Cell research · 2025Article
- Mapping effective microRNA pairing beyond the seed using abasic modifications.Nucleic acids research · 2025Article
- The structural basis for RNA slicing by human Argonaute2.Cell reports · 2025Article
- Structural basis for gene silencing by siRNAs in humans.bioRxiv : the preprint server for biology · 2024Article
- Elucidating microRNA-34a organisation within human Argonaute-2 by dynamic nuclear polarisation-enhanced magic angle spinning NMR.Nucleic acids research · 2024Article
- Target cleavage and gene silencing by Argonautes with cityRNAs.Cell reports · 2024Article
- The structural basis for RNA slicing by human Argonaute2.bioRxiv : the preprint server for biology · 2024Article
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Abstract
The RNA-induced silencing complex (RISC), which powers RNA interference (RNAi), consists of a guide RNA and an Argonaute protein that slices target RNAs complementary to the guide. We find that, for different guide-RNA sequences, slicing rates of perfectly complementary bound targets can be surprisingly different (>250-fold range), and that faster slicing confers better knockdown in cells. Nucleotide sequence identities at guide-RNA positions 7, 10, and 17 underlie much of this variation in slicing rates. Analysis of one of these determinants implicates a structural distortion at guide nucleotides 6-7 in promoting slicing. Moreover, slicing directed by different guide sequences has an unanticipated, 600-fold range in 3'-mismatch tolerance, attributable to guides with weak (AU-rich) central pairing requiring extensive 3' complementarity (pairing beyond position 16) to more fully populate the slicing-competent conformation. Together, our analyses identify sequence determinants of RISC activity and provide biochemical and conformational rationale for their action.
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