A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition

doi:10.1128/mSystems.00575-20

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	A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition
	Zhang, Qing 2; Brambilla, Elisa ; Li, Rui 2; Shi, Hualin 2,3; Lagomarsino, Marco Cosentino 4,5,6,7; Sclavi, Bianca 4
刊名	MSYSTEMS
	2020
卷号	5 期号:5 页码:e00575-20
关键词	RNA-POLYMERASE AVAILABILITY ESCHERICHIA-COLI RIBOSOMAL-RNA GENE-EXPRESSION PPGPP EFFICIENCY PROMOTERS SUBUNITS (P)PPGPP REVEALS
ISSN号	2379-5077
DOI	10.1128/mSystems.00575-20
英文摘要	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 beta and beta' 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. IMPORTANCE Exposure of bacteria to sublethal concentrations of antibiotics can lead to bacterial adaptation and survival at higher doses of inhibitors, which in turn can lead to the emergence of antibiotic resistance. The presence of sublethal concentrations of antibiotics targeting translation results in an increase in the amount of ribosomes per cell but nonetheless a decrease in the cells' growth rate. In this work, we have found that inhibition of ribosome activity can result in a decrease in the amount of free RNA polymerase available for transcription, thus limiting the protein expression rate via a different pathway than what was expected. This result can be explained by our observation that long genes, such as those coding for RNA polymerase subunits, have a higher probability of premature translation termination in the presence of ribosome inhibitors, while expression of short ribosomal genes is affected less, consistent with their increased concentration.
学科主题	Microbiology
语种	英语
内容类型	期刊论文
源URL	[http://ir.itp.ac.cn/handle/311006/27140]
专题	理论物理研究所_理论物理所1978-2010年知识产出
作者单位	1.Ist Nazl Fis Nucl, Milan, Italy 2.ENS Paris Saclay, LBPA, UMR CNRS 8113, Cachan, France 3.Chinese Acad Sci, Inst Theoret Phys, CAS Key Lab Theoret Phys, Beijing, Peoples R China 4.Univ Chinese Acad Sci, Sch Phys Sci, Beijing, Peoples R China 5.Sorbonne Univ, LCQB, UMR CNRS 7238, Paris, France 6.FIRC Inst Mol Oncol, IFOM, Milan, Italy 7.Univ Milan, Dipartimento Fis, Milan, Italy
推荐引用方式 GB/T 7714	Zhang, Qing,Brambilla, Elisa,Li, Rui,et al. A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition[J]. MSYSTEMS,2020,5(5):e00575-20.
APA	Zhang, Qing,Brambilla, Elisa,Li, Rui,Shi, Hualin,Lagomarsino, Marco Cosentino,&Sclavi, Bianca.(2020).A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition.MSYSTEMS,5(5),e00575-20.
MLA	Zhang, Qing,et al."A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition".MSYSTEMS 5.5(2020):e00575-20.