MODELING THE REGULATION OF BACTERIAL GENES PRODUCING PROTEINS THAT STRONGLY INFLUENCE GROWTH

A theoretical method for comparing the performance of rival models of bacterial genetic regulation is presented. The particular difficulties involved in describing the regulated synthesis of proteins that stron gly influence cell growth are identified, and the method is specifical ly designed to treat such cases. The method employs a mathematical des cription of intrinsic perturbations occurring during exponential growt h to test the performance of regulatory models. Specific models of tra nscriptional and translational regulation are inserted into a general gene-expression framework in order to determine their control response s. Applying this approach to examine the regulation of RNA polymerase synthesis in Escherichia coli provides support for the hypothesis that rpoB translation is regulated by cooperative binding of multiple RNA polymerase molecules to the mRNA. The framework is of a sufficiently g eneral form that the method can be used to study mechanisms involved i n controlling synthesis of any bacterial protein. (C) 1994 John Wiley & Sons, Inc.