Principles of gene regulation quantitatively connect DNA to RNA and proteins in bacteria.

Rohan Balakrishnan, Matteo Mori, Igor Segota, Zhongge Zhang, Ruedi Aebersold, Christina Ludwig, Terence Hwa

Science (New York, N.Y.) 2022 Dec 09

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Protein concentrations are set by a complex interplay between gene-specific regulatory processes and systemic factors, including cell volume and shared gene expression machineries. Elucidating this interplay is crucial for discerning and designing gene regulatory systems. We quantitatively characterized gene-specific and systemic factors that affect transcription and translation genome-wide for Escherichia coli across many conditions. The results revealed two design principles that make regulation of gene expression insulated from concentrations of shared machineries: RNA polymerase activity is fine-tuned to match translational output, and translational characteristics are similar across most messenger RNAs (mRNAs). Consequently, in bacteria, protein concentration is set primarily at the promoter level. A simple mathematical formula relates promoter activities and protein concentrations across growth conditions, enabling quantitative inference of gene regulation from omics data.

Citation

Rohan Balakrishnan, Matteo Mori, Igor Segota, Zhongge Zhang, Ruedi Aebersold, Christina Ludwig, Terence Hwa. Principles of gene regulation quantitatively connect DNA to RNA and proteins in bacteria. Science (New York, N.Y.). 2022 Dec 09;378(6624):eabk2066