Cell growth is driven by the synthesis of proteins, genes, and other cellular components. Defining processes that limit biosynthesis rates is fundamental for understanding the determinants of cell physiology. Here, we analyze the consequences of engineering cells to express extremely high levels of mCherry proteins, as a tool to define limiting processes that fail to adapt upon increasing biosynthetic demands. Protein-burdened cells were transcriptionally and phenotypically similar to mutants of the Mediator, a transcription coactivator complex. However, our binding data suggest that the Mediator was not depleted from endogenous promoters. Burdened cells showed an overall increase in the abundance of the majority of endogenous transcripts, except for highly expressed genes. Our results, supported by mathematical modeling, suggest that wild-type cells transcribe highly expressed genes at the maximal possible rate, as defined by the transcription machinery’s physical properties. We discuss the possible cellular benefit of maximal transcription rates to allow a coordinated optimization of cell size and cell growth.

细胞生长是由蛋白质，基因和其他细胞成分的合成驱动的。定义限制生物合成速率的过程对于理解细胞生理学的决定因素至关重要。在这里，我们分析了工程细胞表达极高水平的mCherry蛋白的后果，以此作为定义不能适应不断增长的生物合成需求的限制性过程的工具。蛋白质负担沉重的细胞在转录和表型上类似于介体（转录共激活复合物）的突变体。但是，我们的结合数据表明介体未从内源性启动子中耗竭。除了高度表达的基因外，大多数内源转录本的负担都显示出负担沉重的细胞总体增加。我们的结果得到数学建模的支持，提示野生型细胞以转录机的物理特性所定义的最大可能转录高表达基因。我们讨论最大转录率可能对细胞的好处，以允许细胞大小和细胞生长的协调优化。