Borkowski Olivier, Goelzer Anne, Schaffer Marc, Calabre Magali, Mäder Ulrike, Aymerich Stéphane, Jules Matthieu, Fromion Vincent
Micalis Institute, INRA AgroParisTech Université Paris-Saclay, Jouy-en-Josas, 78350, France MaIAGE, INRA Université Paris-Saclay, Jouy-en-Josas, 78350, France.
MaIAGE, INRA Université Paris-Saclay, Jouy-en-Josas, 78350, France.
Mol Syst Biol. 2016 May 17;12(5):870. doi: 10.15252/msb.20156608.
Complex regulatory programs control cell adaptation to environmental changes by setting condition-specific proteomes. In balanced growth, bacterial protein abundances depend on the dilution rate, transcript abundances and transcript-specific translation efficiencies. We revisited the current theory claiming the invariance of bacterial translation efficiency. By integrating genome-wide transcriptome datasets and datasets from a library of synthetic gfp-reporter fusions, we demonstrated that translation efficiencies in Bacillus subtilis decreased up to fourfold from slow to fast growth. The translation initiation regions elicited a growth rate-dependent, differential production of proteins without regulators, hence revealing a unique, hard-coded, growth rate-dependent mode of regulation. We combined model-based data analyses of transcript and protein abundances genome-wide and revealed that this global regulation is extensively used in B. subtilis We eventually developed a knowledge-based, three-step translation initiation model, experimentally challenged the model predictions and proposed that a growth rate-dependent drop in free ribosome abundance accounted for the differential protein production.
复杂的调控程序通过设定特定条件下的蛋白质组来控制细胞对环境变化的适应。在平衡生长过程中,细菌蛋白质丰度取决于稀释率、转录本丰度和转录本特异性翻译效率。我们重新审视了当前声称细菌翻译效率不变的理论。通过整合全基因组转录组数据集和来自合成绿色荧光蛋白报告基因融合文库的数据集,我们证明枯草芽孢杆菌的翻译效率从缓慢生长到快速生长下降了四倍之多。翻译起始区域引发了无调节因子情况下蛋白质的生长速率依赖性差异产生,从而揭示了一种独特的、硬编码的、生长速率依赖性调节模式。我们结合了全基因组转录本和蛋白质丰度的基于模型的数据分析,发现这种全局调节在枯草芽孢杆菌中被广泛使用。我们最终开发了一个基于知识的三步翻译起始模型,对模型预测进行了实验验证,并提出游离核糖体丰度的生长速率依赖性下降是蛋白质差异产生的原因。