基因调控的原理定量地连接细菌中的DNA与RNA和蛋白质
美国加州大学圣迭戈分校Terence Hwa课题组发现,基因调控的原理定量地连接细菌中的DNA与RNA和蛋白质。2022年12月9日出版的《科学》杂志发表了这项成果。
研究人员对影响大肠杆菌在许多条件下全基因组转录和翻译的基因特异性和系统性因素进行了定量描述。研究结果揭示了两个设计原则,使基因表达的调控与共享机器的浓度绝缘。RNA聚合酶的活性被微调来匹配翻译输出,而翻译的特点在大多数信使RNA(mRNA)中是相似的。因此,在细菌中,蛋白质浓度主要是在启动子水平上设定的。一个简单的数学公式将不同生长条件下的启动子活性和蛋白质浓度联系起来,从而能够从全局数据中定量推断出基因调控。
据介绍,蛋白质浓度是由基因特异性调控过程和系统因素(包括细胞体积和共享基因表达机制)之间复杂的相互作用而确定的。阐明这种相互作用对于辨别和设计基因调控系统至关重要。
附:英文原文
Title: Principles of gene regulation quantitatively connect DNA to RNA and proteins in bacteria
Author: Rohan Balakrishnan, Matteo Mori, Igor Segota, Zhongge Zhang, Ruedi Aebersold, Christina Ludwig, Terence Hwa
Issue&Volume: 2022-12-09
Abstract: 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.
DOI: abk2066
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