The DEAD-box helicase DDX3 substitutes for the cap-binding protein eIF4E to promote compartmentalized translation initiation of the HIV-1 genomic RNA

Nucleic Acids Res. 2013 Jul;41(12):6286-99. doi: 10.1093/nar/gkt306. Epub 2013 Apr 28.


Here, we show a novel molecular mechanism promoted by the DEAD-box RNA helicase DDX3 for translation of the HIV-1 genomic RNA. This occurs through the adenosine triphosphate-dependent formation of a translation initiation complex that is assembled at the 5' m(7)GTP cap of the HIV-1 mRNA. This is due to the property of DDX3 to substitute for the initiation factor eIF4E in the binding of the HIV-1 m(7)GTP 5' cap structure where it nucleates the formation of a core DDX3/PABP/eIF4G trimeric complex on the HIV-1 genomic RNA. By using RNA fluorescence in situ hybridization coupled to indirect immunofluorescence, we further show that this viral ribonucleoprotein complex is addressed to compartmentalized cytoplasmic foci where the translation initiation complex is assembled.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cell Compartmentation
  • Cytoplasmic Granules / chemistry
  • DEAD-box RNA Helicases / analysis
  • DEAD-box RNA Helicases / physiology*
  • Eukaryotic Initiation Factor-4E / metabolism
  • Genome, Viral
  • HIV-1 / genetics*
  • HIV-1 / physiology
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Peptide Chain Initiation, Translational*
  • RNA Caps / metabolism
  • RNA, Viral / analysis
  • RNA, Viral / biosynthesis*
  • Virus Replication


  • Eukaryotic Initiation Factor-4E
  • RNA Caps
  • RNA, Viral
  • Adenosine Triphosphate
  • DDX3X protein, human
  • DEAD-box RNA Helicases