eIF4F is a thermo-sensing regulatory node in the translational heat shock response

Mol Cell. 2024 May 2;84(9):1727-1741.e12. doi: 10.1016/j.molcel.2024.02.038. Epub 2024 Mar 27.


Heat-shocked cells prioritize the translation of heat shock (HS) mRNAs, but the underlying mechanism is unclear. We report that HS in budding yeast induces the disassembly of the eIF4F complex, where eIF4G and eIF4E assemble into translationally arrested mRNA ribonucleoprotein particles (mRNPs) and HS granules (HSGs), whereas eIF4A promotes HS translation. Using in vitro reconstitution biochemistry, we show that a conformational rearrangement of the thermo-sensing eIF4A-binding domain of eIF4G dissociates eIF4A and promotes the assembly with mRNA into HS-mRNPs, which recruit additional translation factors, including Pab1p and eIF4E, to form multi-component condensates. Using extracts and cellular experiments, we demonstrate that HS-mRNPs and condensates repress the translation of associated mRNA and deplete translation factors that are required for housekeeping translation, whereas HS mRNAs can be efficiently translated by eIF4A. We conclude that the eIF4F complex is a thermo-sensing node that regulates translation during HS.

Keywords: biomolecular condensates; budding yeast; eIF4A; eIF4F; eIF4G; heat shock; mRNPs; stress granules; thermosensor; translation.

Publication types

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

MeSH terms

  • Eukaryotic Initiation Factor-4A / genetics
  • Eukaryotic Initiation Factor-4A / metabolism
  • Eukaryotic Initiation Factor-4E / genetics
  • Eukaryotic Initiation Factor-4E / metabolism
  • Eukaryotic Initiation Factor-4F* / genetics
  • Eukaryotic Initiation Factor-4F* / metabolism
  • Eukaryotic Initiation Factor-4G* / genetics
  • Eukaryotic Initiation Factor-4G* / metabolism
  • Gene Expression Regulation, Fungal
  • Heat-Shock Response* / genetics
  • Poly(A)-Binding Proteins*
  • Protein Binding
  • Protein Biosynthesis*
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • Ribonucleoproteins* / genetics
  • Ribonucleoproteins* / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism


  • Saccharomyces cerevisiae Proteins
  • Eukaryotic Initiation Factor-4F
  • RNA, Messenger
  • Eukaryotic Initiation Factor-4G
  • Ribonucleoproteins
  • Eukaryotic Initiation Factor-4E
  • Eukaryotic Initiation Factor-4A
  • messenger ribonucleoprotein
  • pab1 protein, S cerevisiae
  • RNA, Fungal
  • Poly(A)-Binding Proteins