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

ABSTRACT: 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.

ORGANISM(S): Escherichia coli

PROVIDER: GSE182100 | GEO | 2022/10/13

REPOSITORIES: GEO

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Project description:Eukaryotic cells are constantly challenged by the presence of reactive oxygen species, which play an important role in aging and human disease progression. In particular, acute oxidative stress can lead to extensive damage to cellular DNA, proteins, and lipids and can trigger a response that remodels the transcriptional and translational state of the cell. Although a number of previous studies have profiled the relative changes in mRNA and protein and more studies revealing the dynamics of transcription and translation in response to stress are starting to emerge, a quantitative view of this response has been lacking. Here, we have applied quantitative methods to characterize the time dynamics of mRNA and protein levels in the oxidative stress response of the fission yeast Schizosaccharomyces pombe, which has allowed us to perform dynamic modeling of responsive genes in units of copies per cell. Analysis of the resulting time dynamics provided a new genome-wide view of the scale, timing and rates of transcription and translation in the transient response. The majority of dynamic genes were observed to be responsive in their mRNA or protein levels alone implying extensive translational regulation. Nevertheless, modeling of genes with responsive mRNA and protein levels showed that protein levels could, in a majority of these cases, be accurately predicted with constant translation and decay rates while a minority benefited from explicit translation delay parameters. A number of independent features, e.g. measures of codon bias, ribosome occupancy, etc., were found to be less correlated to maximally perturbed protein levels than steady-state levels. Codon bias measures were more correlated than mRNA levels to quantitative protein levels at both perturbed and un-perturbed states. Measures of translation activity, on the other hand, were only significantly correlated at steady state. In total 32 samples: 11 for stressed time series R1, 11 for stressed time series R2, 5 for control time series C1 and 5 for control time series C2

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

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