Global and gene-specific translational regulation in Escherichia coli across different conditions

How well mRNA transcript levels represent protein abundances has been a controversial issue. Particularly across different environments, correlations between mRNA and protein exhibit remarkable variability from gene to gene. Translational regulation is likely to be one of the key factors contributing to mismatches between mRNA level and protein abundance. Here, we quantified genome-wide transcriptome and relative translation efficiency (RTE) under 12 different conditions in Escherichia coli. By quantifying the mRNA-RTE correlation both across genes and across conditions, we uncovered a diversity of gene-specific translational regulations, cooperating with transcriptional regulations, in response to carbon (C), nitrogen (N), and phosphate (P) limitations. Intriguingly, we found that many genes regulating translation are themselves subject to translational regulation, suggesting possible direct feedbacks. Furthermore, we observed that genes with similar expression patterns share similar codon usage. Utilizing a random forest model, we confirmed that codon usage contributes to condition-dependent translational regulation. These findings broaden the understanding of translational regulation under environmental changes, and provide novel strategies for the control of translation in synthetic biology. Overall design: Ribosome profiling and RNA-seq of E. coli cells under 12 different conditions