The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic Networks to Genomic Studies

Control of transcription in bacteria is achieved at many levels, including regulation of transcription initiation and termination, as well as the availability and stability of mRNAs. While some of these mechanisms have been extensively studied and seem to be tightly controlled, transcription termination is often strikingly inefficient. Why such a central process should be inefficient is unclear, although in several cases transcriptional read-through has been reported to benefit the cell. Our aim is to investigate this process and to elucidate the role(s) of transcriptional read-through in bacterial gene regulation as well as its impact on the dynamics of genetic networks. Our approach utilizes established simple synthetic genetic networks, in which individual parameters such as induction, repression and transcriptional termination can be easily manipulated and their influence on transcription individually assessed. This experimental setting allows us to address the question of the effect of transcriptional read-through in an environment with clearly defined inputs and outputs. We plan to assess the influence of modifying termination efficiency on characteristic phenotypes and overall fitness in Escherichia coli and Bacillus subtilis. Understanding the role of transcriptional readthrough will help elucidate the effect of gene order on overall phenotypes.

This project has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° 628377.