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 particukar difficulties involved in describing the regulated synthesis of proteins that strongly influence cell growth are identiied, and the method is specifically designed to treat such cases. The method employs a mathematical description of intrinsic perturbations occurring during exponential growth to test the performance of regulatory models. Specific models of transcriptional and translational regulation are inserted into a general gene-expression framework in order to determine their control responses. Applying thhis approach to examine the regulation of RNA polymerase synthesis in Eschericia 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 general form that the method can be used to study mechanisms involved in controlling synthesis of any bacterial protein. (c) 1994 John Wiley & Sons, Inc.