ArticleMolecular cell2019
Structural Basis for Target-Directed MicroRNA Degradation.
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 166 papers.
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Who cites it
166 citing papers in PubMed, 239 citations in OpenAlex.
- Canonical and non-canonical miRNA degradation shapes state transitions and stemness in breast cancer.The EMBO journal · 2026Article
- Understanding the biological limits of hybridization-dependent siRNA off-target interactions.Molecular therapy. Nucleic acids · 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
- Catalytic activation of human Argonaute 2 requires RNA duplex deformation.Nature structural & molecular biology · 2026Article
- Structural basis for RISC assembly of human Argonaute2.Molecular cell · 2026Article
- CLASHub is an integrated database and analytical platform for microRNA-target interactions.Nature communications · 2026Article
- A viral noncoding RNA is a master regulator of gene expression that defines host cell identity and function.Nucleic acids research · 2026Article
- A lncRNA drives developmentally timed decay of all members of an essential microRNA family.Genes & development · 2026Article
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- Divalent siRNA for prion disease.Nucleic acids research · 2026Article
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- mRNA 3' UTRs direct microRNA degradation to participate in imprinted gene networks and regulate growth.Genes & development · 2026Article
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- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
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- The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation.bioRxiv : the preprint server for biology · 2026Article
- The Role of MicroRNAs in Mitochondrial Homeostasis and their Involvement in the Pathogenesis of Obesity and Metabolic Syndrome: A Focus on MicroRNAs.Current medicinal chemistry · 2026Review
- A unifying model for microRNA-guided silencing of messenger RNAs.Nature communications · 2025Article
- Viral non-coding RNAs hijack host Pumilio proteins to regulate host transcripts.bioRxiv : the preprint server for biology · 2025Article
106 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
MicroRNAs (miRNAs) broadly regulate gene expression through association with Argonaute (Ago), which also protects miRNAs from degradation. However, miRNA stability is known to vary and is regulated by poorly understood mechanisms. A major emerging process, termed target-directed miRNA degradation (TDMD), employs specialized target RNAs to selectively bind to miRNAs and induce their decay. Here, we report structures of human Ago2 (hAgo2) bound to miRNAs and TDMD-inducing targets. miRNA and target form a bipartite duplex with an unpaired flexible linker. hAgo2 cannot physically accommodate the RNA, causing the duplex to bend at the linker and display the miRNA 3' end for enzymatic attack. Altering 3' end display by changing linker flexibility, changing 3' end complementarity, or mutationally inducing 3' end release impacts TDMD efficiency, leading to production of distinct 3'-miRNA isoforms in cells. Our results uncover the mechanism driving TDMD and reveal 3' end display as a key determinant regulating miRNA activity via 3' remodeling and/or degradation.
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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.