The DEAD-Box RNA Helicase DDX3 Interacts with NF-κB Subunit p65 and Suppresses p65-Mediated Transcription

PLoS One. 2016 Oct 13;11(10):e0164471. doi: 10.1371/journal.pone.0164471. eCollection 2016.

Abstract

RNA helicase family members exhibit diverse cellular functions, including in transcription, pre-mRNA processing, RNA decay, ribosome biogenesis, RNA export and translation. The RNA helicase DEAD-box family member DDX3 has been characterized as a tumour-associated factor and a transcriptional co-activator/regulator. Here, we demonstrate that DDX3 interacts with the nuclear factor (NF)-κB subunit p65 and suppresses NF-κB (p65/p50)-mediated transcriptional activity. The downregulation of DDX3 by RNA interference induces the upregulation of NF-κB (p65/p50)-mediated transcription. The regulation of NF-κB (p65/p50)-mediated transcriptional activity was further confirmed by the expression levels of its downstream cytokines, such as IL-6 and IL-8. Moreover, the binding of the ATP-dependent RNA helicase domain of DDX3 to the N-terminal Rel homology domain (RHD) of p65 is involved in the inhibition of NF-κB-regulated gene transcription. In summary, the results suggest that DDX3 functions to suppress the transcriptional activity of the NF-κB subunit p65.

MeSH terms

  • DEAD-box RNA Helicases / antagonists & inhibitors
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • E-Selectin / genetics
  • E-Selectin / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Genes, Reporter
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Immunoprecipitation
  • Interleukin-6 / analysis
  • Interleukin-8 / analysis
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism*
  • Transcription, Genetic
  • Up-Regulation

Substances

  • E-Selectin
  • Interleukin-6
  • Interleukin-8
  • RNA, Small Interfering
  • Transcription Factor RelA
  • DDX3X protein, human
  • DEAD-box RNA Helicases

Grants and funding

This work was supported by the China NSFC grants (81130083, 81271817 and 31221061) (http://www.nsfc.gov.cn/) and the Fundamental Research Funds for the Central Universities (2042016kf0140). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.