ArticleNucleic acids research2015
Slicer-independent mechanism drives small-RNA strand separation during human RISC assembly.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
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- Structural basis for RISC assembly of human Argonaute2.Molecular cell · 2026Article
- Delivery of miR-25802 via Small Vesicles Protects Against Mitochondrial Injury, Oxidative Stress, and Neuroinflammation in Alzheimer's Disease.Molecular neurobiology · 2026Article
- RNA Therapeutics: Delivery Problems and Solutions-A Review.Pharmaceutics · 2025Review
- A guide to the biogenesis and functions of endogenous small non-coding RNAs in animals.Nature reviews. Molecular cell biology · 2025Review
- Catalytic residues of microRNA Argonautes play a modest role in microRNA star strand destabilization in C. elegans.Nucleic acids research · 2024Article
- Phosphorylation of AGO2 by TBK1 Promotes the Formation of Oncogenic miRISC in NSCLC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- The catalytic activity of microRNA Argonautes plays a modest role in microRNA star strand destabilization inbioRxiv : the preprint server for biology · 2024Article
- A specific type of Argonaute phosphorylation regulates binding to microRNAs during C. elegans development.Cell reports · 2022Article
- Engineering miRNA features into siRNAs: Guide-strand bulges are compatible with gene repression.Molecular therapy. Nucleic acids · 2022Article
- The life and death of RNA across temperatures.Computational and structural biotechnology journal · 2022Review
- DELLA proteins BnaA6.RGA and BnaC7.RGA negatively regulate fatty acid biosynthesis by interacting with BnaLEC1s in Brassica napus.Plant biotechnology journal · 2021Article
- The regulatory impact of RNA-binding proteins on microRNA targeting.Nature communications · 2021Article
- Mechanistic analysis of the enhanced RNAi activity by 6-mCEPh-purine at the 5' end of the siRNA guide strand.RNA (New York, N.Y.) · 2021Article
- Effective and Accurate Gene Silencing by a Recombinant AAV-Compatible MicroRNA Scaffold.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Review
- Mechanistic Insights into MicroRNA-Mediated Gene Silencing.Cold Spring Harbor perspectives in biology · 2019Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small RNA silencing is mediated by the effector RNA-induced silencing complex (RISC) that consists of an Argonaute protein (AGOs 1-4 in humans). A fundamental step during RISC assembly involves the separation of two strands of a small RNA duplex, whereby only the guide strand is retained to form the mature RISC, a process not well understood. Despite the widely accepted view that 'slicer-dependent unwinding' via passenger-strand cleavage is a prerequisite for the assembly of a highly complementary siRNA into the AGO2-RISC, here we show by careful re-examination that 'slicer-independent unwinding' plays a more significant role in human RISC maturation than previously appreciated, not only for a miRNA duplex, but, unexpectedly, for a highly complementary siRNA as well. We discovered that 'slicer-dependency' for the unwinding was affected primarily by certain parameters such as temperature and Mg(2+). We further validate these observations in non-slicer AGOs (1, 3 and 4) that can be programmed with siRNAs at the physiological temperature of humans, suggesting that slicer-independent mechanism is likely a common feature of human AGOs. Our results now clearly explain why both miRNA and siRNA are found in all four human AGOs, which is in striking contrast to the strict small-RNA sorting system in Drosophila.
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