Regulation of GTP hydrolysis prior to ribosomal AUG selection during eukaryotic translation initiation

Romit Majumdar, Umadas Maitra

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Genetic studies in yeast have shown that the translation initiation factor eIF5 plays an important role in the selection of the AUG start codon. In order to ensure translation fidelity, the hydrolysis of GTP bound to the 40S preinitiation complex (40S·Met-tRNAi·eIF2·GTP), promoted by eIF5, must occur only when the complex has selected the AUG start codon. However, the mechanism that prevents the eIF5-promoted GTP hydrolysis, prior to AUG selection by the ribosomal machinery, is not known. In this work, we show that the presence of initiation factors eIF1, eIF1A and eIF3 in the 40S preinitiation complex (40S·eIF1·eIF1A·eIF3·Met- tRNAi·eIF2·GTP) and the subsequent binding of the preinitiation complex to eIF4F bound at the 5′-cap structure of mRNA are necessary for preventing eIF5-promoted hydrolysis of GTP in the 40S preinitiation complex. This block in GTP hydrolysis is released upon AUG selection by the 40S preinitiation complex. These results, taken together, demonstrate the biochemical requirements for regulation of GTP hydrolysis and its coupling to the AUG selection process during translation initiation.

Original languageEnglish (US)
Pages (from-to)3737-3746
Number of pages10
JournalEMBO Journal
Volume24
Issue number21
DOIs
StatePublished - Nov 2 2005

Fingerprint

Guanosine Triphosphate
Hydrolysis
Peptide Initiation Factors
Initiator Codon
RNA Caps
Yeast
Machinery
Yeasts

Keywords

  • GTP hydrolysis
  • Ribosomes
  • Translation initiation
  • Translation initiation factor eIF5

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Regulation of GTP hydrolysis prior to ribosomal AUG selection during eukaryotic translation initiation. / Majumdar, Romit; Maitra, Umadas.

In: EMBO Journal, Vol. 24, No. 21, 02.11.2005, p. 3737-3746.

Research output: Contribution to journalArticle

Majumdar, Romit ; Maitra, Umadas. / Regulation of GTP hydrolysis prior to ribosomal AUG selection during eukaryotic translation initiation. In: EMBO Journal. 2005 ; Vol. 24, No. 21. pp. 3737-3746.
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