RNA interference may suppress stress granule formation by preventing argonaute 2 recruitment

Qiang Lou, Yanzhong Hu, Yanfang Ma, Zheng Dong

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

RNA-induced silencing complex (RISC) is formed during RNA interference (RNAi), whereas stress granules (SG) are assembled in response to cellular stress. Here, we demonstrate an interesting connection between RISC and SG that may involve argonaute 2 (Ago2), a core component of RISC. We analyzed SG induction by arsenite, the commonly used SG inducer. SG formation was suppressed in heat shock transcription factor 1 (Hsf1) or hypoxia-inducible factor-1β (Hif1β) shRNA-transfected cells but not in Hsf1 or Hif1β-knockout cells, suggesting that RNAi per se (rather than gene deficiency) may account for the suppressive effect on SG. In support, the suppressive effect of RNAi on SG formation was reversed by the RISC-loading inhibitor aurintricar-boxylic acid. In non-RNAi cells, arsenite induced the accumulation of Ago2 in SGs as shown by its colocalization and coimmunoprecipita-tion with SG proteins, but Ago2 was not recruited to SG in the cells with RNAi. Consistently, arsenite induced the dissociation of Ago2 from RISC proteins in non-RNAi cells but not in RNAi cells. CRISPR-Cas9-medicated ablation of Ago2 attenuated SG formation during arsenite treatment, suggesting a critical role of Ago2 in SG assembly. Together, these results indicate that RISC and SG may compete for some key components, such as Ago2. In response to cellular stress, Ago2 is recruited for SG assembly; however, during RNAi, Ago2 is held in RISC, becoming unavailable for SG formation.

Original languageEnglish (US)
Pages (from-to)C81-C91
JournalAmerican Journal of Physiology - Cell Physiology
Volume316
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • Argonaute 2
  • Arsenite
  • RNA interference
  • RNA-induced silencing complex
  • Stress granule

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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