Distinct mechanisms coordinate transcription and translation under carbon and nitrogen starvation in Escherichia coli

Abstract

Bacteria adapt to environmental stress by producing proteins that provide stress protection. However, stress can severely perturb the kinetics of gene expression, disrupting protein production. Here, we characterized how Escherichia coli mitigates such perturbations under nutrient stress through the kinetic coordination of transcription and translation. We observed that, when translation became limiting under nitrogen starvation, transcription elongation slowed accordingly. This slowdown was mediated by (p)ppGpp, the alarmone whose primary role is thought to be promoter regulation. This kinetic coordination by (p)ppGpp was critical for the robust synthesis of gene products. Surprisingly, under carbon starvation, (p)ppGpp was dispensable for robust synthesis. Characterization of the underlying kinetics revealed that under carbon starvation, transcription became limiting, and translation aided transcription elongation. This mechanism naturally coordinated transcription with translation, alleviating the need for (p)ppGpp as a mediator. These contrasting mechanisms for coordination resulted in the condition-dependent effects of (p)ppGpp on global protein synthesis and starvation survival. Our findings reveal a kinetic aspect of gene expression plasticity, establishing (p)ppGpp as a condition-dependent global effector of gene expression.

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Fig. 1: Effects of C- and N starvation on gene expression kinetics.
Fig. 2: Characterization of transcription elongation and translation elongation.
Fig. 3: Contrasting effects of (p)ppGpp on transcription and translation kinetics under N- and C starvation.
Fig. 4: Condition-dependent effects of (p)ppGpp on global protein synthesis activity and cell survival.

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Acknowledgements

We thank M. Cashel, R.L. Gourse and J. Wang for helpful discussions and kindly sharing strains with us. This work was funded by Research Corporation for Science Advancement (24097) and the Human Frontier Science Program (RGY0072/2015).

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S.I., D.L., B.R.P. and M.K. designed the study. S.I., D.L. and B.R.P. performed experiments. S.I. D.K. and B.R.P. analysed the data. M.K. wrote the manuscript.

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Correspondence to Minsu Kim.

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Iyer, S., Le, D., Park, B.R. et al. Distinct mechanisms coordinate transcription and translation under carbon and nitrogen starvation in Escherichia coli. Nat Microbiol 3, 741–748 (2018). https://doi.org/10.1038/s41564-018-0161-3

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