title: An in vivo control map for the eukaryotic mRNA translation machinery.
abstract: Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non-intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non-stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNA(i) to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than-average 5'untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5'UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis.
authors: School of Life Sciences, University of Warwick, Coventry, UK.
authors: Helena
authors: H
authors: Firczuk
authors: Shichina
authors: S
authors: Kannambath
authors: Jürgen
authors: J
authors: Pahle
authors: Amy
authors: A
authors: Claydon
authors: Robert
authors: R
authors: Beynon
authors: John
authors: J
authors: Duncan
authors: Hans
authors: H
authors: Westerhoff
authors: Pedro
authors: P
authors: Mendes
authors: John Eg
authors: JE
authors: McCarthy
mesh_terms: D003198:Computer Simulation; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D039562:Eukaryotic Initiation Factor-4F / Q000235:genetics / Q000378:metabolism; D020440:Gene Duplication; D015966:Gene Expression Regulation, Fungal; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D054682:Ribosome Subunits, Small, Eukaryotic / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015852:Eukaryotic Initiation Factor-2; D039562:Eukaryotic Initiation Factor-4F; D029543:Nucleocytoplasmic Transport Proteins; D010454:Peptide Termination Factors; D012333:RNA, Messenger; C080775:SUP45 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer; C492382:DBP5 protein, S cerevisiae; D053487:DEAD-box RNA Helicases