The DHX33 RNA Helicase Promotes mRNA Translation Initiation

Mol Cell Biol. 2015 Sep 1;35(17):2918-31. doi: 10.1128/MCB.00315-15. Epub 2015 Jun 22.


DEAD/DEAH box RNA helicases play essential roles in numerous RNA metabolic processes, such as mRNA translation, pre-mRNA splicing, ribosome biogenesis, and double-stranded RNA sensing. Herein we show that a recently characterized DEAD/DEAH box RNA helicase, DHX33, promotes mRNA translation initiation. We isolated intact DHX33 protein/RNA complexes in cells and identified several ribosomal proteins, translation factors, and mRNAs. Reduction of DHX33 protein levels markedly reduced polyribosome formation and caused the global inhibition of mRNA translation that was rescued with wild-type DHX33 but not helicase-defective DHX33. Moreover, we observed an accumulation of mRNA complexes with the 80S ribosome in the absence of functional DHX33, consistent with a stalling in initiation, and DHX33 more preferentially promoted structured mRNA translation. We conclude that DHX33 functions to promote elongation-competent 80S ribosome assembly at the late stage of mRNA translation initiation. Our results reveal a newly recognized function of DHX33 in mRNA translation initiation, further solidifying its central role in promoting cell growth and proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DEAD-box RNA Helicases / genetics*
  • Eukaryotic Initiation Factor-4A / genetics
  • Female
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / metabolism
  • HeLa Cells
  • Humans
  • Peptide Chain Initiation, Translational / genetics*
  • Polyribosomes / genetics*
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Helicases / genetics
  • RNA Interference
  • RNA, Messenger / genetics*
  • RNA, Small Interfering


  • RNA, Messenger
  • RNA, Small Interfering
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
  • DHX29 protein, human
  • Eukaryotic Initiation Factor-4A
  • DHX33 protein, human
  • EIF4A3 protein, human
  • DEAD-box RNA Helicases
  • RNA Helicases