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

Nucleic Acids Res. 2011 Apr;39(7):2727-41. doi: 10.1093/nar/gkq1216. Epub 2010 Dec 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins
  • Cell Line
  • Cytoplasmic Granules / chemistry
  • Cytoplasmic Granules / metabolism
  • Eukaryotic Initiation Factor-2 / analysis
  • Eukaryotic Initiation Factor-2 / metabolism*
  • Humans
  • Oligonucleotides / chemistry
  • Protein Transport
  • RNA Interference*
  • Stress, Physiological


  • AGO2 protein, human
  • Argonaute Proteins
  • Eukaryotic Initiation Factor-2
  • Oligonucleotides