The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex

Shang Yi Chiu, Fabrice Lejeune, Aparna R Sertil, Lynne E. Maquat

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

The bulk of cellular proteins derive from the translation of eukaryotic translation initiation factor (eIF)4E-bound mRNA. However, recent studies of nonsense-mediated mRNA decay (NMD) indicate that cap-binding protein (CBP)80-bound mRNA, which is a precursor to eIF4E-bound mRNA, can also be translated during a pioneer round of translation. Here, we report that the pioneer round, which can be assessed by measuring NMD, is not inhibited by 4E-BP1, which is known to inhibit steady-state translation by competing with eIF4G for binding to eIF4E. Therefore, at least in this way, the pioneer round of translation is distinct from steady-state translation. eIF4GI, poly(A)-binding protein (PABP)1, eIF3, eIF4AI, and eIF2α coimmunopurify with both CBP80 and eIF4E, which suggests that each factor functions in both modes of translation. Consistent with roles for PABP1 and eIF2α in the pioneer round of translation, PABP-interacting protein 2, which is known to destabilize PABP1 binding to poly(A) and inhibit steady-state translation, as well as inactive eIF2α, which is also known to inhibit steady-state translation, also inhibit NMD. Polysome profiles indicate that CBP80-bound mRNAs are translated less efficiently than their eIF4E-bound counterparts.

Original languageEnglish (US)
Pages (from-to)745-754
Number of pages10
JournalGenes and Development
Volume18
Issue number7
DOIs
StatePublished - Apr 1 2004
Externally publishedYes

Fingerprint

Nonsense Mediated mRNA Decay
Poly(A)-Binding Proteins
Messenger RNA
RNA Cap-Binding Proteins
Eukaryotic Initiation Factor-4E
Eukaryotic Initiation Factors
Poly A
Polyribosomes
Protein Biosynthesis
Proteins

Keywords

  • Nonsense-mediated mRNA decay
  • Pioneer translation initiation complex
  • Steady-state translation initiation complex

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. / Chiu, Shang Yi; Lejeune, Fabrice; Sertil, Aparna R; Maquat, Lynne E.

In: Genes and Development, Vol. 18, No. 7, 01.04.2004, p. 745-754.

Research output: Contribution to journalArticle

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