Principles of gene regulation quantitatively connect DNA to RNA and proteins in bacteria
作者:Rohan Balakrishnan, Matteo Mori, Igor Segota, Zhongge Zhang, Ruedi Aebersold, Christina Ludwig, Terence Hwa
Science:2022/12/09
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.
蛋白质浓度由基因特异调控过程和系统因素之间的互作确定。本研究定量表征了在多种条件下影响大肠杆菌全基因组转录和翻译的基因特异以及系统因素,总结出两大原则:RNA聚合酶活性被精准调节以匹配翻译输出,而翻译特征在大部分信使RNA中相似(mRNA)。结果表明细菌中的蛋白质浓主要设定在启动子水平。