Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in stress granule assembly and stress response

Jing Wen Shih, Wei Ting Wang, Tsung Yuan Tsai, Chu Yun Kuo, Hao Kang Li, Yan Hwa Wu Lee

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Upon environmental insults, SGs (stress granules) aid cell survival by serving as sites of translational silencing. RNA helicase DDX3 was reported to associate with SGs. However, its role in SG physiology remains undefined. We have demonstrated previously that DDX3 acts as an eIF4E (eukaryotic initiation factor 4E)-inhibitory protein to suppress translation. In the present study, we indentified the SG marker PABP1 [poly(A)-binding protein 1] as another direct interaction partner of DDX3. We established various stimuli as novel stressors that direct DDX3 with eIF4E and PABP1 into SGs, but not to processing bodies. Interestingly, down-regulation of DDX3 interfered with SG assembly, led to nuclear accumulation of PABP1 and reduced cell viability following stress. Conversely, supplementation with a shRNA (short hairpin RNA)-resistant DDX3 restored SG formation, the translocation of PABP1 into SGs and cell survival. Notably, the SG-inducing capacity of DDX3 is independent of its ATPase and helicase activities, but mapped to the eIF4E-binding region. Moreover, the eIF4E-binding-defective mutant DDX3 was impaired in its SG-inducing ability and protective effect on cell survival under adverse conditions. All together, the present study has characterized DDX3 as a pivotal SG-nucleating factor and illustrates co-ordinative roles for DDX3, eIF4E and PABP1 in integrating environmental stress with translational regulation.

Original languageEnglish
Pages (from-to)119-129
Number of pages11
JournalBiochemical Journal
Volume441
Issue number1
DOIs
Publication statusPublished - Jan 1 2012
Externally publishedYes

Fingerprint

Poly(A)-Binding Proteins
Eukaryotic Initiation Factor-4E
RNA Helicases
Cell Survival
Poly(A)-Binding Protein II
Cells
Small Interfering RNA
Adenosine Triphosphatases
Down-Regulation
Physiology
Proteins

Keywords

  • DDX3
  • DEAD box RNA helicase
  • Eukaryotic initiation factor 4E-inhibitory protein (eIF4E-inhibitory protein)
  • Processing body
  • Stress granule
  • Stress response

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in stress granule assembly and stress response. / Shih, Jing Wen; Wang, Wei Ting; Tsai, Tsung Yuan; Kuo, Chu Yun; Li, Hao Kang; Wu Lee, Yan Hwa.

In: Biochemical Journal, Vol. 441, No. 1, 01.01.2012, p. 119-129.

Research output: Contribution to journalArticle

Shih, Jing Wen ; Wang, Wei Ting ; Tsai, Tsung Yuan ; Kuo, Chu Yun ; Li, Hao Kang ; Wu Lee, Yan Hwa. / Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in stress granule assembly and stress response. In: Biochemical Journal. 2012 ; Vol. 441, No. 1. pp. 119-129.
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