ArticleeLife2022
Target binding triggers hierarchical phosphorylation of human Argonaute-2 to promote target release.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- Argonaute and small RNAs in the nucleus: Mediators of gene silencing and activation.Molecular therapy. Nucleic acids · 2026Review
- Structural dynamics between Argonaute-2 and CK1α promote target RNA release in microRNA-mediated silencing.bioRxiv : the preprint server for biology · 2026Article
- CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleosts.The EMBO journal · 2025Article
- Dysregulation of AGO2-miRNA dynamics underlies the AGO2-associated Lessel-Kreienkamp syndrome.Nucleic acids research · 2025Article
- Partners in Silencing: Decoding the Mammalian Argonaute Interactome.Non-coding RNA · 2025Review
- Importance of an N-terminal structural switch in the distinction between small RNA-bound and free ARGONAUTE.Nature structural & molecular biology · 2025Article
- The structural basis for RNA slicing by human Argonaute2.Cell reports · 2025Article
- Inorganic arsenic modulates cell apoptosis by regulating Argonaute 2 expression via the p53 pathway.Toxicology research · 2025Article
- CLK2 Condensates Reorganize Nuclear Speckles and Induce Intron Retention.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The structural basis for RNA slicing by human Argonaute2.bioRxiv : the preprint server for biology · 2024Article
- To kill a microRNA: emerging concepts in target-directed microRNA degradation.Nucleic acids research · 2024Review
- An essential role for the RNA helicase DDX6 in NMDA receptor-dependent gene silencing and dendritic spine shrinkage.Scientific reports · 2024Article
- Recent progress in miRNA biogenesis and decay.RNA biology · 2024Review
- Casein kinase 1 and 2 phosphorylate Argonaute proteins to regulate miRNA-mediated gene silencing.EMBO reports · 2023Article
- The Role of microRNAs in Epigenetic Regulation of Signaling Pathways in Neurological Pathologies.International journal of molecular sciences · 2023Review
- Oncogenic K-Ras suppresses global miRNA function.Molecular cell · 2023Article
- A tiny loop in the Argonaute PIWI domain tunes small RNA seed strength.EMBO reports · 2023Article
- Transcriptome-Wide Analysis of microRNA-mRNA Correlations in Tissue Identifies microRNA Targeting Determinants.Non-coding RNA · 2023Article
- Target binding triggers hierarchical phosphorylation of human Argonaute-2 to promote target release.eLife · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Argonaute (Ago) proteins play a central role in post-transcriptional gene regulation through RNA interference (RNAi). Agos bind small RNAs (sRNAs) including small interfering RNAs (siRNAs) and microRNAs (miRNAs) to form the functional core of the RNA-induced silencing complex (RISC). The sRNA is used as a guide to target mRNAs containing either partially or fully complementary sequences, ultimately leading to downregulation of the corresponding proteins. It was previously shown that the kinase CK1α phosphorylates a cluster of residues in the eukaryotic insertion (EI) of Ago, leading to the alleviation of miRNA-mediated repression through an undetermined mechanism. We show that binding of miRNA-loaded human Ago2 to target RNA with complementarity to the seed and 3' supplementary regions of the miRNA primes the EI for hierarchical phosphorylation by CK1α. The added negative charges electrostatically promote target release, freeing Ago to seek out additional targets once it is dephosphorylated. The high conservation of potential phosphosites in the EI suggests that such a regulatory strategy may be a shared mechanism for regulating miRNA-mediated repression.
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What OpenQuestion holds
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.