title: The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.
abstract: Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism.
authors.affiliation: Université de Toulouse; INSA, UPS, INP, 135 Avenue de Rangueil, F-31077, Toulouse, France.|INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, LISBP, F-31400, Toulouse, France.|CNRS, UMR5504, F-31400, Toulouse, France.|Inria Grenoble-Rhône-Alpes, 655 avenue de l'Europe, 38334, Montbonnot Cedex, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Morin
authors.affiliation: Inria Grenoble-Rhône-Alpes, 655 avenue de l'Europe, 38334, Montbonnot Cedex, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Ropers
authors.affiliation: Université de Toulouse; INSA, UPS, INP, 135 Avenue de Rangueil, F-31077, Toulouse, France.|INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, LISBP, F-31400, Toulouse, France.|CNRS, UMR5504, F-31400, Toulouse, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Letisse
authors.affiliation: Université de Toulouse; INSA, UPS, INP, 135 Avenue de Rangueil, F-31077, Toulouse, France.|INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, LISBP, F-31400, Toulouse, France.|CNRS, UMR5504, F-31400, Toulouse, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Laguerre
authors.affiliation: Université de Toulouse; INSA, UPS, INP, 135 Avenue de Rangueil, F-31077, Toulouse, France.|INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, LISBP, F-31400, Toulouse, France.|CNRS, UMR5504, F-31400, Toulouse, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Portais
authors.affiliation: Université de Toulouse; INSA, UPS, INP, 135 Avenue de Rangueil, F-31077, Toulouse, France.|INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, LISBP, F-31400, Toulouse, France.|CNRS, UMR5504, F-31400, Toulouse, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Cocaign-Bousquet
authors.affiliation: Université de Toulouse; INSA, UPS, INP, 135 Avenue de Rangueil, F-31077, Toulouse, France.|INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, LISBP, F-31400, Toulouse, France.|CNRS, UMR5504, F-31400, Toulouse, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Enjalbert
mesh_terms: D002244:Carbon / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D009154:Mutation; D025221:Phosphofructokinases / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: C093587:CsrA protein, E coli; D029968:Escherichia coli Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D002244:Carbon; D006003:Glycogen; D025221:Phosphofructokinases