Synergistic regulation of transcription and translation in Escherichia coli revealed by co-directional increases in mRNA concentration and translation efficiency

Translational regulation was investigated at the genome scale in Escherichia coli cells. Using the polysome profiling method, the ribosome occupancy (RO) and ribosome density (RD) of different mRNA copies were determined for several hundred mRNAs during the exponential and stationary phases, providing the most complete characterisation of such regulation in E. coli. Although for most genes, nearly all mRNAs (>90%) were undergoing translation, they were loaded with far fewer than the theoretical maximum number of ribosomes, suggesting translation limitation at the initiation step. Multiple linear regression was used to identify key intrinsic factors involved in the genome-wide regulation of RO and RD (i.e., open reading frame GC%, protein function and localisation). Unexpectedly, mRNA concentration, a factor that depends on cell physiology, was predicted to positively regulate RO and RD during the exponential and stationary phases. Using a set of selected genes controlled by an inducible promoter, we confirmed that increasing the mRNA concentration upon transcription induction led to increases in both RO and ribosome load. The fact that this relationship between mRNA concentration and translation parameters was also effective when E. coli cells naturally adapted to carbon source changes demonstrates its physiological relevance. This work demonstrates that translation regulation is positively controlled by transcript availability. This new mechanism contributes to the co-directional regulation of transcription and translation with synergistic effects on gene expression, and provides a systemic understanding of E. coli cell function. We reported RNA-seq data for translatome experiments performed in E. coli MG1655 in two growth phases (exponential phase and stationary phase). In each phase, translatome experiments consisting of 7 RNA-seq for each polysomal fraction from A to G were carried out in triplicates.