title: An integrated approach reveals regulatory controls on bacterial translation elongation.
abstract: Ribosomes elongate at a nonuniform rate during translation. Theoretical models and experiments disagree on the in vivo determinants of elongation rate and the mechanism by which elongation rate affects protein levels. To resolve this conflict, we measured transcriptome-wide ribosome occupancy under multiple conditions and used it to formulate a whole-cell model of translation in E. coli. Our model predicts that elongation rates at most codons during nutrient-rich growth are not limited by the intracellular concentrations of aminoacyl-tRNAs. However, elongation pausing during starvation for single amino acids is highly sensitive to the kinetics of tRNA aminoacylation. We further show that translation abortion upon pausing accounts for the observed ribosome occupancy along mRNAs during starvation. Abortion reduces global protein synthesis, but it enhances the translation of a subset of mRNAs. These results suggest a regulatory role for aminoacylation and abortion during stress, and our study provides an experimentally constrained framework for modeling translation.
authors.affiliation: Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: asubram@fas.harvard.edu.
authors.forename: Arvind R
authors.initials: AR
authors.lastname: Subramaniam
authors.affiliation: Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Zid
authors.affiliation: Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: erin_oshea@harvard.edu.
authors.forename: Erin K
authors.initials: EK
authors.lastname: O'Shea
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D008954:Models, Biological; D010441:Peptide Chain Elongation, Translational; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000378:metabolism
chemical_list: D000596:Amino Acids