Assembly of an active translation initiation factor complex by a viral protein

Derek Walsh, Ian Mohr*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Recruitment of the 40S ribosome to the 5′ end of a eukaryotic mRNA requires assembly of translation initiation factors eIF4E, the cap-binding protein, together with eIF4A and eIF4G into a complex termed eIF4F. While the translational repressor 4E-BP1 regulates binding of eIF4E to eIF4G, the forces required to construct an eIF4F complex remain unidentified. Here, we establish that the herpes simplex virus-1 (HSV-1) ICP6 polypeptide associates with eIF4G to promote eIF4F complex assembly. Strikingly, release of eIF4E from the 4E-BP1 repressor is insufficient to drive complex formation, suggesting that ICP6 is an eIF4F-assembly chaperone. This is the first example of a translation initiation factor-associated protein that promotes active complex assembly and defines a new, controllable step in the initiation of translation. Homology of the N-terminal, eIF4G-binding segment of ICP6 with cellular chaperones suggest that factors capable of interacting with eIF4G and promoting eIF4F complex assembly may play important roles in a variety of processes where translation complexes need to be remodeled or assembled on populations of newly synthesized or derepressed mRNAs, including development, differentiation, and the response to a broad spectrum of environmental cues.

Original languageEnglish (US)
Pages (from-to)461-472
Number of pages12
JournalGenes and Development
Issue number4
StatePublished - Feb 15 2006


  • HSV-1 replication
  • Translational control
  • eIF4E phosphorylation
  • eIF4F assembly

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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