DNA supercoiling - a global transcriptional regulator for enterobacterial growth?

• Published in: Nature reviews. Microbiology 2005-02, Vol.3 (2), p.157-169
• Main Authors: Travers, Andrew, Muskhelishvili, Georgi
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Deoxyribonucleic acid; DNA; DNA, Bacterial - chemistry; DNA, Bacterial - physiology; DNA, Superhelical - chemistry; DNA, Superhelical - physiology; E coli; Escherichia coli; Escherichia coli - genetics; Escherichia coli - growth & development; Gene Expression Regulation, Bacterial; Infectious Diseases; Life Sciences; Medical Microbiology; Microbiology; Mutation; Nucleic Acid Conformation; Nutrient availability; Nutrient balance; Parasitology; Protein synthesis; Proteins; review-article; Ribonucleic acid; RNA; RNA polymerase; RNA, Untranslated - metabolism; Transcription, Genetic; Transfer RNA; Virology
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro1088

Key Points An important aspect of growth control in enterobacteria is regulation of production of the translational machinery. Stable RNA (rRNA and tRNA) promoters are unusually dependent on high negative superhelicity for optimal expression. This superhelicity facilitates the wrapping of DNA around the polymerase and enhances its untwisting in the −10 region. Stringent control and growth-rate control of stable RNA transcription are mechanistically distinct and dependent on different, but overlapping, elements of promoter structure. Growth-rate control of a promoter and its dependence on negative superhelicity are correlated, while ppGpp, the effector of the stringent response, is antagonized by high negative superhelicity. The transcription factor FIS acts as a topological homeostat for some stable RNA promoters by locally constraining superhelicity, thereby decreasing the sensitivity of expression to fluctuations in superhelical density. The effective, or available, superhelicity of promoter DNA is determined by competition between abundant nucleoid-associated proteins, which constrain negative supercoils, and RNA polymerase, thereby balancing the compaction and availability of DNA. Transcription regulation during growth-phase transitions is correlated with changes in negative superhelicity, adaptive changes in the RNA polymerase that alter the responses of transcription machinery to supercoiling, and changes in the composition of the nucleoid-associated proteins that affect the availability of negative supercoils. The global control of transcription throughout the life cycle of Escherichia coli can be formalized as an interacting network of gene products and low-molecular-weight effectors that control RNA polymerase selectivity and effective superhelicity. A fundamental principle of exponential bacterial growth is that no more ribosomes are produced than are necessary to support the balance between nutrient availability and protein synthesis. Although this conclusion was first expressed more than 40 years ago, a full understanding of the molecular mechanisms involved remains elusive and the issue is still controversial. There is currently agreement that, although many different systems are undoubtedly involved in fine-tuning this balance, an important control, and in our opinion perhaps the main control, is regulation of the rate of transcription initiation of the stable (ribosomal and transfer) RNA transcriptons. In this review, we argue that regulatio