Regulation of GTP hydrolysis prior to ribosomal AUG selection during eukaryotic translation initiation
Open Access
- 13 October 2005
- journal article
- Published by Springer Nature in The EMBO Journal
- Vol. 24 (21) , 3737-3746
- https://doi.org/10.1038/sj.emboj.7600844
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.Keywords
This publication has 36 references indexed in Scilit:
- A Conformational Change in the Eukaryotic Translation Preinitiation Complex and Release of eIF1 Signal Recognition of the Start CodonMolecular Cell, 2005
- The Molecular Mechanics of Eukaryotic TranslationAnnual Review of Biochemistry, 2004
- The Yeast Eukaryotic Initiation Factor 4G (eIF4G) HEAT Domain Interacts with eIF1 and eIF5 and Is Involved in Stringent AUG SelectionMolecular and Cellular Biology, 2003
- Mammalian Translation Initiation Factor eIF1 Functions with eIF1A and eIF3 in the Formation of a Stable 40 S Preinitiation ComplexJournal of Biological Chemistry, 2003
- Eukaryotic Translation Initiation Factor 5 Functions as a GTPase-activating ProteinJournal of Biological Chemistry, 2001
- Mutational Analysis of Mammalian Translation Initiation Factor 5 (eIF5): Role of Interaction between the β Subunit of eIF2 and eIF5 in eIF5 Function In Vitro and In VivoMolecular and Cellular Biology, 2000
- eIF4 Initiation Factors: Effectors of mRNA Recruitment to Ribosomes and Regulators of TranslationAnnual Review of Biochemistry, 1999
- Specific Interaction of Eukaryotic Translation Initiation Factor 5 (eIF5) with the β-Subunit of eIF2Journal of Biological Chemistry, 1997
- Function of Eukaryotic Translation Initiation Factor 1A (eIF1A) (Formerly Called eIF-4C) in Initiation of Protein SynthesisJournal of Biological Chemistry, 1997
- Purification and Characterization of Bacterially Expressed Mammalian Translation Initiation Factor 5 (eIF-5): Demonstration That eIF-5 Forms a Specific Complex with eIF-2Biochemistry, 1994