ArticleCell reports2025
The structural basis for RNA slicing by human Argonaute2.
Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- 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
- 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
- Experimentally Tuned Protein-RNA Rosetta Score Function using Bayesian Optimization.bioRxiv : the preprint server for biology · 2026Article
- UsingbioRxiv : the preprint server for biology · 2026Article
- Article
- Structural basis for RISC assembly of human Argonaute2.Molecular cell · 2026Article
- Molecular Dynamics Simulation-Assisted siRNA Design for Dual-Ubiquitinated SKP2 Silencing via Ago2 Anchoring in Breast Cancer.ACS omega · 2026Article
- Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.Nucleic acids research · 2026Article
- Article
- mRNA 3' UTRs direct microRNA degradation to participate in imprinted gene networks and regulate growth.Genes & development · 2026Article
- Structural dynamics between Argonaute-2 and CK1α promote target RNA release in microRNA-mediated silencing.bioRxiv : the preprint server for biology · 2026Article
- Structural insights into disease-associated mutations in the microRNA processing machinery.Experimental & molecular medicine · 2026Review
- PAIRNet: Predicting PIWI cleavage specificity via position-aware RNA interaction modeling.PLoS computational biology · 2026Article
- The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation.bioRxiv : the preprint server for biology · 2026Article
- Presence of phosphodiester backbone, but not nucleobases, in the guide's 3' terminal region is necessary for RISC loading and target cleavage in vitro and in vivo.Nucleic acids research · 2026Article
- mRNA 3' UTRs direct microRNA degradation to participate in imprinted gene networks and regulate growth.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
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4 authors.
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Abstract
Argonaute (AGO) proteins associate with guide RNAs to form complexes that slice transcripts that pair to the guide. This slicing drives post-transcriptional gene silencing through RNA interference (RNAi), which is essential for many eukaryotes and the basis for new clinical therapies. Despite this importance, structural information on eukaryotic AGOs in a fully paired, slicing-competent conformation-hypothesized to be intrinsically unstable-has been lacking. Here, we present the cryogenic electron microscopy structure of a human AGO-guide complex bound to a fully paired target, revealing structural rearrangements that enable this conformation. Critically, the N domain of AGO rotates to allow the RNA full access to the central channel and forms contacts that license rapid slicing. Moreover, a conserved loop in the PIWI domain secures the RNA near the active site to enhance slicing rate and specificity. These results explain how AGO accommodates targets possessing pairing specificity typically observed in biological and clinical slicing substrates.
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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.