ArticleThe EMBO journal2019
Beyond the seed: structural basis for supplementary microRNA targeting by human Argonaute2.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
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Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Computational meta-analysis of ribosomal RNA fragments: potential targets and interaction mechanisms.Nucleic acids research · 2021Pooled it
- Engineered human Argonaute 2 for targeted C-to-U RNA base editing.Nature biotechnology · 2026Article
- 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
- Seedless 3' pairing enables miR-17 family miRNAs to seize let-7 target sites.Nucleic acids research · 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
- The AGO2 adaptor LIMD1 expands the functional and evolutionary reach of microRNA targeting.Science advances · 2026Article
- Structural basis for RISC assembly of human Argonaute2.Molecular cell · 2026Article
- Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.Nucleic acids research · 2026Article
- Article
- Structural dynamics between Argonaute-2 and CK1α promote target RNA release in microRNA-mediated silencing.bioRxiv : the preprint server for biology · 2026Article
- RIMap-RISC: a transcriptome-wide database of structurally modeled human microRNA interactions.Genome biology · 2026Article
- Biochemical principles of miRNA targeting in flies.Nature communications · 2026Article
- The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation.bioRxiv : the preprint server for biology · 2026Article
- MicroRNA-phytochemical interactome targeting thioredoxin-interacting protein: a narrative review at the nexus of RNA therapeutics, cancer biology, and metabolic regulation.Frontiers in oncology · 2026Review
- Review
- A unifying model for microRNA-guided silencing of messenger RNAs.Nature communications · 2025Article
- Viral sequence analysis of chronic hepatitis B patients treated with the siRNA JNJ-73763989 in phase II clinical trials.JHEP reports : innovation in hepatology · 2025Article
- Dysregulation of AGO2-miRNA dynamics underlies the AGO2-associated Lessel-Kreienkamp syndrome.Nucleic acids research · 2025Article
- Functional microRNA targeting without seed pairing.Nucleic acids research · 2025Article
51 more citing papers are in PubMed but not listed here.
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4 authors.
Funding
Abstract
microRNAs (miRNAs) guide Argonaute proteins to mRNAs targeted for repression. Target recognition occurs primarily through the miRNA seed region, composed of guide (g) nucleotides g2-g8. However, nucleotides beyond the seed are also important for some known miRNA-target interactions. Here, we report the structure of human Argonaute2 (Ago2) engaged with a target RNA recognized through both miRNA seed and supplementary (g13-g16) regions. Ago2 creates a "supplementary chamber" that accommodates up to five miRNA-target base pairs. Seed and supplementary chambers are adjacent to each other and can be bridged by an unstructured target loop of 1-15 nucleotides. Opening of the supplementary chamber may be constrained by tension in the miRNA 3' tail, as increases in miRNA length stabilize supplementary interactions. Contrary to previous reports, we demonstrate that optimal supplementary interactions can increase target affinity > 20-fold. These results provide a mechanism for extended miRNA targeting, suggest a function for 3' isomiRs in tuning miRNA targeting specificity, and indicate that supplementary interactions may contribute more to target recognition than is widely appreciated.
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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.