title: A genome-scale integration and analysis of Lactococcus lactis translation data.
abstract: Protein synthesis is a template polymerization process composed by three main steps: initiation, elongation, and termination. During translation, ribosomes are engaged into polysomes whose size is used for the quantitative characterization of translatome. However, simultaneous transcription and translation in the bacterial cytosol complicates the analysis of translatome data. We established a procedure for robust estimation of the ribosomal density in hundreds of genes from Lactococcus lactis polysome size measurements. We used a mechanistic model of translation to integrate the information about the ribosomal density and for the first time we estimated the protein synthesis rate for each gene and identified the rate limiting steps. Contrary to conventional considerations, we find significant number of genes to be elongation limited. This number increases during stress conditions compared to optimal growth and proteins synthesized at maximum rate are predominantly elongation limited. Consistent with bacterial physiology, we found proteins with similar rate and control characteristics belonging to the same functional categories. Under stress conditions, we found that synthesis rate of regulatory proteins is becoming comparable to proteins favored under optimal growth. These findings suggest that the coupling of metabolic states and protein synthesis is more important than previously thought.
authors.affiliation: Laboratory of Computational Systems Biotechnology, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland ; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Racle
authors.forename: Flora
authors.initials: F
authors.lastname: Picard
authors.forename: Laurence
authors.initials: L
authors.lastname: Girbal
authors.forename: Muriel
authors.initials: M
authors.lastname: Cocaign-Bousquet
authors.forename: Vassily
authors.initials: V
authors.lastname: Hatzimanikatis
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D016680:Genome, Bacterial / Q000235:genetics*; D013294:Lactococcus lactis / Q000235:genetics* / Q000378:metabolism*; D011132:Polyribosomes / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis
chemical_list: D001426:Bacterial Proteins