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Nucleic Acids Research Advance Access originally published online on May 5, 2007
Nucleic Acids Research 2007 35(11):3573-3580; doi:10.1093/nar/gkm283
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Nucleic Acids Research, 2007, Vol. 35, No. 11 3573-3580
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Computational Biology

Distributed control for recruitment, scanning and subunit joining steps of translation initiation

Padchanee Sangthong, John Hughes and John E. G. McCarthy*

Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK

*To whom correspondence should be addressed. Tel: +44-161-200-8916; Fax: +44-161-200-8918; Email: john.mccarthy{at}manchester.ac.uk

Received March 12, 2007. Revised March 29, 2007. Accepted April 11, 2007.

Protein synthesis utilizes a large proportion of the available free energy in the eukaryotic cell and must be precisely controlled, yet up to now there has been no systematic rate control analysis of the in vivo process. We now present a novel study of rate control by eukaryotic translation initiation factors (eIFs) using yeast strains in which chromosomal eIF genes have been placed under the control of the tetO7 promoter system. The results reveal that, contrary to previously published reports, control of the initiation pathway is distributed over all of the eIFs, whereby rate control (the magnitude of their respective component control coefficients) follows the order: eIF4G > eIF1A > eIF4E > eIF5B. The apparent rate control effects of eIFs observed in standard cell-free extract experiments, on the other hand, do not accurately reflect the steady state in vivo data. Overall, this work establishes the first quantitative control framework for the study of in vivo eukaryotic translation.


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