eIF4G is required for the pioneer round of translation in mammalian cells

Fabrice Lejeune, Aparna C. Ranganathan, Lynne E. Maquat

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Nonsense-mediated mRNA decay (NMD) in mammalian cells targets cap-binding protein 80 (CBPBO)-bound mRNA during or after a pioneer round of translation. It is unknown whether eukaryotic translation initiation factor 4G (eIF4G) functions in the pioneer round. We show that baculovirus-produced CBP80 and CBP20 independently interact with eIF4GI. The interactions between eIF4G and the heterodimer CBP80/20 suggest that eIF4G has a function in the pioneer initiation complex rather than merely a presence during remodeling to the steady-state complex. First, NMD is inhibited upon eIF4G cleavage by HIV-2 or poliovirus 2A pro tease. Second, eIF4GI coimmunopurifies with pre-mRNA, indicating that it associates with transcripts before the pioneer round. Third, eIF4G immunopurifies with Upf NMD factors and eIF4AIII, which are constituents of the pioneer translation initiation complex. We propose a model in which eIF4G serves to connect CBP80/20 with other initiation factors during the pioneer round of translation.

Original languageEnglish (US)
Pages (from-to)992-1000
Number of pages9
JournalNature Structural and Molecular Biology
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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