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A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition.
mSystems ( IF 6.4 ) Pub Date : 2020-09-08 , DOI: 10.1128/msystems.00575-20
Qing Zhang 1 , Elisa Brambilla 1 , Rui Li 2 , Hualin Shi 2, 3 , Marco Cosentino Lagomarsino 4 , Bianca Sclavi 5
Affiliation  

In bacterial cells, inhibition of ribosomes by sublethal concentrations of antibiotics leads to a decrease in the growth rate despite an increase in ribosome content. The limitation of ribosomal activity results in an increase in the level of expression from ribosomal promoters; this can deplete the pool of RNA polymerase (RNAP) that is available for the expression of nonribosomal genes. However, the magnitude of this effect remains to be quantified. Here, we use the change in the activity of constitutive promoters with different affinities for RNAP to quantify the change in the concentration of free RNAP. The data are consistent with a significant decrease in the amount of RNAP available for transcription of both ribosomal and nonribosomal genes. Results obtained with different reporter genes reveal an mRNA length dependence on the amount of full-length translated protein, consistent with the decrease in ribosome processivity affecting more strongly the translation of longer genes. The genes coding for the β and β' subunits of RNAP are among the longest genes in the Escherichia coli genome, while the genes coding for ribosomal proteins are among the shortest genes. This can explain the observed decrease in transcription capacity that favors the expression of genes whose promoters have a high affinity for RNAP, such as ribosomal promoters.

中文翻译:

转录能力的下降限制了翻译抑制后的增长率。

在细菌细胞中,尽管核糖体含量增加,但亚致死浓度的抗生素对核糖体的抑制会导致生长速度下降。核糖体活性的限制导致核糖体启动子表达水平的增加;这会耗尽可用于非核糖体基因表达的 RNA 聚合酶 (RNAP) 库。然而,这种影响的程度仍有待量化。在这里,我们使用对 RNAP 具有不同亲和力的组成型启动子活性的变化来量化游离 RNAP 浓度的变化。该数据与可用于核糖体和非核糖体基因转录的 RNAP 量显着减少一致。使用不同报告基因获得的结果揭示了 mRNA 长度依赖于全长翻译蛋白的数量,这与核糖体持续合成能力的降低对更长基因的翻译产生更强烈的影响一致。编码 RNAP 的 β 和 β' 亚基的基因是最长的基因之一。大肠杆菌基因组,而编码核糖体蛋白的基因是最短的基因之一。这可以解释观察到的转录能力下降,这有利于其启动子对 RNAP 具有高亲和力的基因的表达,例如核糖体启动子。
更新日期:2020-09-09
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