ITP OpenIR  > SCI期刊论文
Zhang, Qing1; Brambilla, Elisa; Li, Rui1; Shi, Hualin1,2; Lagomarsino, Marco Cosentino3,4,5,6; Sclavi, Bianca3
A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition
Source PublicationMSYSTEMS
AbstractIn 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.
Cooperation Status国际
Subject AreaMicrobiology
MOST Discipline CatalogueMicrobiology
Indexed BySCIE
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Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Affiliation1.ENS Paris Saclay, LBPA, UMR CNRS 8113, Cachan, France
2.Chinese Acad Sci, Inst Theoret Phys, CAS Key Lab Theoret Phys, Beijing, Peoples R China
3.Univ Chinese Acad Sci, Sch Phys Sci, Beijing, Peoples R China
4.Sorbonne Univ, LCQB, UMR CNRS 7238, Paris, France
5.FIRC Inst Mol Oncol, IFOM, Milan, Italy
6.Univ Milan, Dipartimento Fis, Milan, Italy
7.Ist Nazl Fis Nucl, Milan, Italy
Recommended Citation
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.
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