ArticleThe EMBO journal2013
The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing.
Article in The EMBO journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed, 226 citations in OpenAlex.
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- Protocol using AGO-APP for isolation and sequencing of argonaute-bound miRNAs in specific neuronal subtypes of the mouse brain.STAR protocols · 2026Article
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- In vivo AGO-APP for cell-type- and compartment-specific miRNA profiling in the mouse brain.Cell reports methods · 2026Article
- Disease-related miRNA mutations are associated with mature miRNA secondary structure changes.Biophysical journal · 2025Article
- Widely conserved miRNAs in buffalo milk extracellular vesicles survive gastrointestinal digestion and potentially target neural and immunomodulatory contexts.Frontiers in nutrition · 2025Article
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- Intracellular delivery of antiviral shRNA using penetratin-based complexes effectively inhibits respiratory syncytial virus replication and host cell apoptosis.Virology journal · 2024Article
- Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference.Nucleic acids research · 2024Article
- Endoplasmic reticulum-targeted delivery of celastrol and PD-L1 siRNA for reinforcing immunogenic cell death and potentiating cancer immunotherapy.Acta pharmaceutica Sinica. B · 2024Article
- StaufenC facilitates utilization of the ERAD pathway to transport dsRNA through the endoplasmic reticulum to the cytosol.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ago2/CAV1 interaction potentiates metastasis via controlling Ago2 localization and miRNA action.EMBO reports · 2024Article
- Functional identification of cis-regulatory long noncoding RNAs at controlled false discovery rates.Nucleic acids research · 2024Article
- An emerging role for the endoplasmic reticulum in stress granule biogenesis.Seminars in cell & developmental biology · 2024Review
- Heat stress promotes Arabidopsis AGO1 phase separation and association with stress granule components.iScience · 2024Article
- Nuclear localization of Argonaute 2 is affected by cell density and may relieve repression by microRNAs.Nucleic acids research · 2024Article
- Next-Cell Hypothesis: Mechanism of Obesity-Associated Carcinogenesis.Advances in experimental medicine and biology · 2024Review
- Dynamics of nucleic acid mobility.Genetics · 2023Article
- An update in the applications of exosomes in cancer theranostics: from research to clinical trials.Journal of cancer research and clinical oncology · 2023Review
81 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite progress in mechanistic understanding of the RNA interference (RNAi) pathways, the subcellular sites of RNA silencing remain under debate. Here we show that loading of lipid-transfected siRNAs and endogenous microRNAs (miRNA) into RISC (RNA-induced silencing complexes), encounter of the target mRNA, and Ago2-mediated mRNA slicing in mammalian cells are nucleated at the rough endoplasmic reticulum (rER). Although the major RNAi pathway proteins are found in most subcellular compartments, the miRNA- and siRNA-loaded Ago2 populations co-sediment almost exclusively with the rER membranes, together with the RISC loading complex (RLC) factors Dicer, TAR RNA binding protein (TRBP) and protein activator of the interferon-induced protein kinase (PACT). Fractionation and membrane co-immune precipitations further confirm that siRNA-loaded Ago2 physically associates with the cytosolic side of the rER membrane. Additionally, RLC-associated double-stranded siRNA, diagnostic of RISC loading, and RISC-mediated mRNA cleavage products exclusively co-sediment with rER. Finally, we identify TRBP and PACT as key factors anchoring RISC to ER membranes in an RNA-independent manner. Together, our findings demonstrate that the outer rER membrane is a central nucleation site of siRNA-mediated RNA silencing.
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