Cell stress is related to re-localization of Argonaute 2 and to decreased RNA interference in human cells
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Various kinds of stress on human cells induce the formation of endogenous stress granules (SGs). Human Argonaute 2 (hAgo2), the catalytic core component of the RNA-induced silencing complex (RISC), can be recruited to SGs as well as P-bodies (PBs) indicating that the dynamic intracellular distribution of hAgo2 in SGs, in PBs or at other sub-cellular sites could be related to the efficiency of the RNA interference (RNAi) machinery. Here, we studied the influence of heat shock, sodium arsenite (NaAsO2), cycloheximide (CHX) and Lipofectamine 2000-mediated transfection of phosphorothioate (PS)-modified oligonucleotides (ON) on the intracellular localization of hAgo2 and the efficiency of RNAi. Fluorescence microscopy and sedimentation analysis of cell fractions indicate stress-induced accumulation of hAgo2 in SGs and the loss of distinctly composed complexes containing hAgo2 or their sub-cellular context. Transfection of cells with PS-ON induces cell stress that is phenotypically similar to the established inducers heat shock and NaAsO2. The intracellular re-distribution of hAgo2 is related to its increased metabolic stability and to decreased RNAi directed by microRNA or by short interfering RNA. Here, we propose a functional model of the relationship between cell stress, translocation of hAgo2 to SGs providing a depot function, and loss of RNAi activity.
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miRISC and target mRNA localize in multiple subcellular compartments including rough endoplasmic reticulum, P-bodies, stress granules, trans-Golgi network, early/late endosomes, multivesicular bodies, lysosomes, mitochondria, and the nucleus.
“miRISC and target mRNA have been observed to localize in multiple subcellular compartments including rough endoplasmic reticulum (rER) (70), processing (P)-bodies (71), stress granules (SG) (72), the trans-Golgi network (TGN), early/late endosomes (73), multivesicular bodies (MVB) (74), lysosomes (74), mitochondria (75, 76), and the nucleus (66, 77) (Figure 2).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [72]
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- Authors
- Detzer, A., Engel, C., Wünsche, W., & Sczakiel, G.
- Affiliations
- University of Lübeck (DE)
- Corresponding author
- Sczakiel, Georg
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-12-08
- Volume
- 39
- Issue
- 7
- Pages
- 2727-2741
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC3074141
- OpenAlex
- W2150833816
- Cited by
- 74
- References
- 59
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 3 · 2019: 8 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 2 · 2013: 7 · 2012: 3
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Philipps-Universität Marburg
- Universität Heidelberg
- University of California, San Diego
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- Argonaute 2, stress granules, P-bodies, RNA interference, RNA-induced silencing complex, cellular stress, subcellular localization, phosphorothioate oligonucleotides, heat shock, sodium arsenite, cycloheximide, microRNA, siRNA, protein stability
- MeSH terms
- Cell Line, Cytoplasmic Granules, Humans, Oligonucleotides, Stress, Physiological, Eukaryotic Initiation Factor-2, Protein Transport, RNA Interference, Argonaute Proteins
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