ArticleMolecular cell2019
Multidomain Convergence of Argonaute during RISC Assembly Correlates with the Formation of Internal Water Clusters.
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 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Structural basis for RISC assembly of human Argonaute2.Molecular cell · 2026Article
- Navigating the next frontier in biomedicine: breakthroughs and insights in nucleic acid therapeutics.Chemical science · 2026Review
- Neurodevelopmental disorder-linked Argonaute mutations permit delayed RISC formation and unusual shortening of miRNAs by 3'→5' trimming.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural and evolutionary determinants of Argonaute function.Nucleic acids research · 2025Article
- Conformational Dynamics of hAgo2 Silencing: Decoding Functional Divergence across Human Argonaute Paralogs.Journal of chemical information and modeling · 2025Article
- Comparative structural insights and functional analysis for the distinct unbound states of Human AGO proteins.Scientific reports · 2025Article
- Article
- Identification ofMolecules (Basel, Switzerland) · 2025Article
- Epigenetic regulation in female reproduction: the impact of m6A on maternal-fetal health.Cell death discovery · 2025Review
- HydraProt: A New Deep Learning Tool for Fast and Accurate Prediction of Water Molecule Positions for Protein Structures.Journal of chemical information and modeling · 2024Article
- Sex-Biased Expression and Response of microRNAs in Neurological Diseases and Neurotrauma.International journal of molecular sciences · 2024Review
- The role of m6A epigenetic modifications in tumor coding and non-coding RNA processing.Cell communication and signaling : CCS · 2023Review
- Determining the defining lengths between mature microRNAs/small interfering RNAs and tinyRNAs.Scientific reports · 2023Article
- Determining the defining lengths between mature microRNAs/small interfering RNAs and tinyRNAs.bioRxiv : the preprint server for biology · 2023Article
- Structural basis for RNA slicing by a plant Argonaute.Nature structural & molecular biology · 2023Article
- The Multiplicity of Argonaute Complexes in Mammalian Cells.The Journal of pharmacology and experimental therapeutics · 2023Review
- A specific type of Argonaute phosphorylation regulates binding to microRNAs during C. elegans development.Cell reports · 2022Article
- miR-155-3p: processing by-product or rising star in immunity and cancer?Open biology · 2022Review
- A Structural View of miRNA Biogenesis and Function.Non-coding RNA · 2022Review
- Construction of a miRNA-mRNA Network Related to Exosomes in Colon Cancer.Disease markers · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Despite the relevance of Argonaute proteins in RNA silencing, little is known about the structural steps of small RNA loading to form RNA-induced silencing complexes (RISCs). We report the 1.9 Å crystal structure of human Argonaute4 with guide RNA. Comparison with the previously determined apo structure of Neurospora crassa QDE2 revealed that the PIWI domain has two subdomains. Binding of guide RNA fastens the subdomains, thereby rearranging the active-site residues and increasing the affinity for TNRC6 proteins. We also identified two water pockets beneath the nucleic acid-binding channel that appeared to stabilize the mature RISC. Indeed, mutating the water-pocket residues of Argonaute2 and Argonaute4 compromised RISC assembly. Simulations predict that internal water molecules are exchangeable with the bulk solvent but always occupy specific positions at the domain interfaces. These results suggest that after guide RNA-driven conformational changes, water-mediated hydrogen-bonding networks tie together the converged domains to complete the functional RISC structure.
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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.