Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity

Elife. 2017 Nov 30;6:e31476. doi: 10.7554/eLife.31476.


eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5'-untranslated regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We show that eIF4A's ATPase activity is markedly stimulated in the presence of the PIC, independently of eIF4E•eIF4G, but dependent on subunits i and g of the heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of recruitment of all mRNAs tested, regardless of their degree of structural complexity. Structures in the 5'-UTR and 3' of the start codon synergistically inhibit mRNA recruitment in a manner relieved by eIF4A, indicating that the factor does not act solely to melt hairpins in 5'-UTRs. Our findings that eIF4A functionally interacts with the PIC and plays important roles beyond unwinding 5'-UTR structure is consistent with a recent proposal that eIF4A modulates the conformation of the 40S ribosomal subunit to promote mRNA recruitment.

Keywords: RNA helicase; S. cerevisiae; biochemistry; biophysics; eIF4A; eIF4F; mRNA recruitment; ribosome; structural biology; translation initiation.

MeSH terms

  • 5' Untranslated Regions
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Eukaryotic Initiation Factor-4E / genetics
  • Eukaryotic Initiation Factor-4E / metabolism
  • Eukaryotic Initiation Factor-4F / metabolism*
  • Eukaryotic Initiation Factor-4G / genetics
  • Eukaryotic Initiation Factor-4G / metabolism
  • Protein Binding
  • Protein Conformation
  • RNA Helicases / metabolism*
  • RNA, Fungal / chemistry*
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • RNA, Messenger / chemistry*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • 5' Untranslated Regions
  • Eukaryotic Initiation Factor-4E
  • Eukaryotic Initiation Factor-4F
  • Eukaryotic Initiation Factor-4G
  • RNA, Fungal
  • RNA, Messenger
  • RPL41 protein, S cerevisiae
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • TIF4631 protein, S cerevisiae
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • RNA Helicases
  • TIF1 protein, S cerevisiae

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.