title: Comparison of repressor and transcriptional attenuator systems for control of amino acid biosynthetic operons.
abstract: In bacteria, expression from amino acid biosynthetic operons is transcriptionally controlled by two main mechanisms with principally different modes of action. When the supply of an amino acid is in excess over demand, its concentration will be high and when the supply is deficient the amino acid concentration will be low. In repressor control, such concentration variations in amino acid pools are used to regulate expression from the corresponding amino acid synthetic operon; a high concentration activates and a low concentration inactivates repressor binding to the operator site on DNA so that initiation of transcription is down or up-regulated, respectively. Excess or deficient supply of an amino acid also speeds or slows, respectively, the rate by which the ribosome translates mRNA base triplets encoding this amino acid. In attenuation of transcription, it is the rate by which the ribosome translates such "own" codons in the leader of an amino acid biosynthetic operon that decides whether the RNA polymerase will continue into the operon, or whether transcription will be aborted (attenuated). If the ribosome rate is fast (excess synthesis of amino acid), transcription will be terminated and if the rate is slow (deficient amino acid supply) transcription will continue and produce more messenger RNAs. Repressor and attenuation control systems have been modelled mathematically so that their behaviour in living cells can be predicted and their system properties compared. It is found that both types of control systems are unexpectedly sensitive when they operate in the cytoplasm of bacteria. In the repressor case, this is because amino acid concentrations are hypersensitive to imbalances between supply and demand. In the attenuation case, the reason is that the rate by which ribosomes translate own codons is hypersensitive to the rate by which the controlled amino acid is synthesised. Both repressor and attenuation mechanisms attain close to Boolean properties in vivo: gene expression is either fully on or fully off except in a small interval around the point where supply and demand of an amino acid are perfectly balanced.Our results suggest that repressors have significantly better intracellular performance than attenuator mechanisms. The reason for this is that repressor, but not attenuator, mechanisms can regulate expression from biosynthetic operons also when transfer RNAs are fully charged with amino acids so that the ribosomes work with maximal speed.
authors.affiliation: Department of Cell and Molecular Biology, BMC, SE-751 24 Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Elf
authors.forename: O G
authors.initials: OG
authors.lastname: Berg
authors.forename: M
authors.initials: M
authors.lastname: Ehrenberg
mesh_terms: D000215:Acylation; D000596:Amino Acids / Q000096:biosynthesis* / Q000235:genetics*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D007700:Kinetics; D008957:Models, Genetic; D009876:Operon / Q000235:genetics*; D014176:Protein Biosynthesis; D012097:Repressor Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D012680:Sensitivity and Specificity; D013269:Stochastic Processes; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D012097:Repressor Proteins; D012321:DNA-Directed RNA Polymerases