Cited by 74RNA Interference and Gene DeliveryRNA Research and SplicingRNA and protein synthesis mechanisms

Cell stress is related to re-localization of Argonaute 2 and to decreased RNA interference in human cells

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Detzer, Anke, Engel, Christina, Wünsche, Winfried, Sczakiel, Georg·2011·Nucleic Acids Research

Abstract

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).”

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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
Published
2010-12-08
Volume
39
Issue
7
Pages
2727-2741
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
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
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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