Article
- The EMBO Journal (2005) 24, 3737 - 3746
- doi:10.1038/sj.emboj.7600844
Published online: 13 October 2005
Subject Category:
Regulation of GTP hydrolysis prior to ribosomal AUG selection during eukaryotic translation initiation
Romit Majumdar1 and Umadas Maitra1
- Department of Developmental and Molecular Biology, Albert Einstein College of Medicine of Yeshiva University, Jack and Pearl Resnick Campus, Bronx, NY, USA
Correspondence to:
Umadas Maitra, Department of Developmental and Molecular Biology, Albert Einstein College of Medicine of Yeshiva University, Jack and Pearl Resnick Campus, Bronx, NY 10461, USA. Tel.: +1 718 430 3505; Fax: +1 718 430 8567; E-mail: maitra@aecom.yu.edu
Received 30 June 2005; Accepted 21 September 2005
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-tRNAieIF2GTP), 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 (40SeIF1eIF1AeIF3Met-tRNAieIF2GTP) 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:
- GTP hydrolysis,
- ribosomes,
- translation initiation,
- translation initiation factor eIF5
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
REVIEWS
Getting the message in protein synthesis. Keystone Symposium on Translational Regulatory Mechanisms
EMBO reports Review (01 Oct 2008)
NEWS AND VIEWS
Nature Structural & Molecular Biology News and Views (01 Feb 2006)
Translation Cinderella factors have a ball
Nature News and Views (27 Aug 1998)
RESEARCH
The EMBO Journal Article (01 May 2001)
The eIF1A C-terminal domain promotes initiation complex assembly, scanning and AUG selection in vivo
The EMBO Journal Article (19 Oct 2005)
