The DEAD-box protein Ded1 modulates translation by the formation and resolution of an eIF4F-mRNA complex

Mol Cell. 2011 Sep 16;43(6):962-72. doi: 10.1016/j.molcel.2011.08.008.

Abstract

The translation, localization, and degradation of cytoplasmic mRNAs are controlled by the formation and rearrangement of their mRNPs. The conserved Ded1/DDX3 DEAD-box protein functions in an unknown manner to affect both translation initiation and repression. We demonstrate that Ded1 first functions by directly interacting with eIF4G to assemble a Ded1-mRNA-eIF4F complex, which accumulates in stress granules. After ATP hydrolysis by Ded1, the mRNP exits stress granules and completes translation initiation. Thus, Ded1 functions both as a repressor of translation, by assembling an mRNP stalled in translation initiation, and as an ATP-dependent activator of translation, by resolving the stalled mRNP. These results identify Ded1 as a translation initiation factor that assembles and remodels an intermediate complex in translation initiation.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Cytoplasmic Granules / metabolism
  • DEAD-box RNA Helicases / chemistry
  • DEAD-box RNA Helicases / metabolism
  • DEAD-box RNA Helicases / physiology*
  • Eukaryotic Initiation Factor-4F / metabolism*
  • Eukaryotic Initiation Factor-4G / metabolism
  • Gene Expression Regulation
  • Models, Genetic
  • Molecular Sequence Data
  • Protein Biosynthesis*
  • RNA, Messenger / metabolism*
  • Ribonucleoproteins / metabolism
  • Ribonucleoproteins / physiology
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Sequence Alignment

Substances

  • Eukaryotic Initiation Factor-4F
  • Eukaryotic Initiation Factor-4G
  • RNA, Messenger
  • Ribonucleoproteins
  • Saccharomyces cerevisiae Proteins
  • messenger ribonucleoprotein
  • Adenosine Triphosphate
  • DED1 protein, S cerevisiae
  • DEAD-box RNA Helicases