title: Distributed control for recruitment, scanning and subunit joining steps of translation initiation.
abstract: 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.
authors.affiliation: Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
authors.forename: Padchanee
authors.initials: P
authors.lastname: Sangthong
authors.forename: John
authors.initials: J
authors.lastname: Hughes
authors.forename: John E G
authors.initials: JE
authors.lastname: McCarthy
mesh_terms: D004318:Doxycycline / Q000494:pharmacology; D039642:Eukaryotic Initiation Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D010442:Peptide Chain Initiation, Translational; D021122:Protein Subunits / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D039642:Eukaryotic Initiation Factors; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D004318:Doxycycline