ArticleMolecular cell2019
High-Throughput Analysis Reveals Rules for Target RNA Binding and Cleavage by AGO2.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
104 citing papers in PubMed, 168 citations in OpenAlex.
- Decoding RNA-protein interactions using high-throughput methods.RNA biology · 2026Review
- Human Argonaute 2 is a programmable targeting domain for RNA editing.Nature biotechnology · 2026Article
- Engineered human Argonaute 2 for targeted C-to-U RNA base editing.Nature biotechnology · 2026Article
- Understanding the biological limits of hybridization-dependent siRNA off-target interactions.Molecular therapy. Nucleic acids · 2026Article
- Review
- Central guide-target pairing activates human Argonaute2 by uncoupling the N-PAZ and MID-PIWI lobes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A High-Throughput Platform for Rapid Adaptation of DNA Aptamers to SARS-CoV-2 Evolution.bioRxiv : the preprint server for biology · 2026Article
- Divalent siRNA for prion disease.Nucleic acids research · 2026Article
- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
- RIMap-RISC: a transcriptome-wide database of structurally modeled human microRNA interactions.Genome biology · 2026Article
- PAIRNet: Predicting PIWI cleavage specificity via position-aware RNA interaction modeling.PLoS computational biology · 2026Article
- Specificity of DNA targeting by RNA-guided pAgo nucleases.Nucleic acids research · 2026Article
- Biochemical principles of miRNA targeting in flies.Nature communications · 2026Article
- Article
- 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
- Therapeutic AASS inhibition by AAV-miRNA rescues glutaric aciduria type I severe phenotype in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The Life of MicroRNAs: Biogenesis, Function and Decay in Cancer.Biomolecules · 2025Review
- A conserved PIWI silencing complex detects piRNA-target engagement.Molecular cell · 2025Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Argonaute proteins loaded with microRNAs (miRNAs) or small interfering RNAs (siRNAs) form the RNA-induced silencing complex (RISC), which represses target RNA expression. Predicting the biological targets, specificity, and efficiency of both miRNAs and siRNAs has been hamstrung by an incomplete understanding of the sequence determinants of RISC binding and cleavage. We applied high-throughput methods to measure the association kinetics, equilibrium binding energies, and single-turnover cleavage rates of mouse AGO2 RISC. We find that RISC readily tolerates insertions of up to 7 nt in its target opposite the central region of the guide. Our data uncover specific guide:target mismatches that enhance the rate of target cleavage, suggesting novel siRNA design strategies. Using these data, we derive quantitative models for RISC binding and target cleavage and show that our in vitro measurements and models predict knockdown in an engineered cellular system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.