CarD contributes to diverse gene expression outcomes throughout the genome of
            <i>Mycobacterium tuberculosis</i>

Zhu, Dennis X; Garner, Ashley L.; Galburt, Eric A.; Stallings, Christina L.

doi:10.1073/pnas.1900176116

Cited by 35 publications

(57 citation statements)

References 49 publications

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“…It localizes to promoter regions where the housekeeping sigma factor resides, directly binds to the RNAP β subunit, stabilizes the open promoter complex, and is required for transcription from rRNA promoters [2,3,5]. Recent work in Mycobacterium tuberculosis using mutants of CarD (the CdnL homolog) unable to bind either RNAP or DNA showed that CdnL can act as an activator or repressor of transcription depending on the stability of the RNAP-promoter complex [7]. M. tuberculosis CarD is essential for growth in culture, persistence in mice, and survival during genotoxic stress and starvation [2,4].…”

Section: Introductionmentioning

confidence: 99%

The conserved transcriptional regulator CdnL is required for metabolic homeostasis and morphogenesis in Caulobacter

et al. 2020

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Section: Introductionmentioning

confidence: 99%

The conserved transcriptional regulator CdnL is required for metabolic homeostasis and morphogenesis in Caulobacter

et al. 2020

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“…Such a www.nature.com/scientificreports www.nature.com/scientificreports/ severe reduction in rRNA operon expression would impact protein synthesis leading to downstream deleterious consequences seen in GreA depleted cell. Previous studies showed that the expression of rRNA in mycobacteria is positively regulated by CarD 28,36 . In GreA_CKD, apart from the reduction in rRNA expression, the expression of CarD was also reduced (Earlier section, Figs.…”

Section: Resultsmentioning

confidence: 98%

“…When CarD was discovered, it was found to be a negative regulator as its depletion led to upregulation of 16 S rRNA 27 . However, in a subsequent study, it was shown to be a global regulator of transcription initiation 28,36 . Trancript analysis of CarD depleated M.smegmatis showed differential regulation of large number of genes including rRNA and translational machinary genes 27 .…”

Section: Discussionmentioning

confidence: 97%

Conditional down-regulation of GreA impacts expression of rRNA and transcription factors, affecting Mycobacterium smegmatis survival

Jha

Udupa

Kumar

et al. 2020

Sci Rep

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Gre, one of the conserved transcription factors in bacteria, modulates RnA polymerase (RnAp) activity to ensure processivity and fidelity of RNA synthesis. Gre factors regulate transcription by inducing the intrinsic-endonucleolytic activity of RnAp, allowing the enzyme to resume transcription from the paused and arrested sites. While Escherichia coli and a number of eubacteria harbor GreA and GreB, genus mycobacteria has a single Gre (GreA). to address the importance of the GreA in growth, physiology and gene expression of Mycobacterium smegmatis, we have constructed a conditional knockdown strain of GreA. the GreA depleted strain exhibited slow growth, drastic changes in cell surface phenotype, cell death, and increased susceptibility to front-line anti-tubercular drugs. transcripts and 2D-gel electrophoresis (2D-PAGE) analysis of the GreA conditional knock-down strain showed altered expression of the genes involved in transcription regulation. Among the genes analysed, expression of RnAp subunits (β, β' and ω), carD, hupB, lsr2, and nusA were affected to a large extent. Severe reduction in the expression of genes of rRnA operon in the knock-down strain reveal a role for GreA in regulating the core components of the translation process. Transcription is the central process in the cell. It is regulated by a variety of proteins at different stages. Many of these regulators control transcription by modulating the RNAP activity. The movement of RNAP along the template often gets interrupted by pauses resulting in backtracked RNAP. During backtracking, RNAP slides backwards along the DNA and the 3′ end of the newly synthesized RNA is disengaged from the active centre 1,2. In order to continue RNA extension from the 3′ end, bacteria have evolved strategies that serve to assist the backtracked RNAP to reinitiate elongation. The newly synthesized 3′ end of RNA is subjected to intrinsic cleavage by RNAP itself 3-6. Gre factors bind to the RNAP and assist transcript-cleavage 1,7-12. The absence of Gre would prolong or even prevent rescuing of backtracked RNAP complexes leading to a pause or arrest of transcription. This would limit overall rate and processivity of transcription and hence cell survival. Although Gre factors or their homologues are conserved in all forms of life, present understanding of their in vivo role in bacteria other than in E. coli is limited. Even in E. coli, a complete understanding of the effect of Gre mutants is hindered because of the presence of two Gre (GreA and GreB) and also the partial redundancy in function by the other secondary channel binding proteins such as DksA, Rnk and TraR 13-15. While GreA cleaves 2-3 nucleotide from 3′ end of RNA, GreB cleaves up to 9 nucleotide fragments. However, how the other secondary channel binding proteins complement their function is not clearly understood. It has been shown that GreA, GreB and DksA are mutually competing and exhibit functional redundancy 15. In E. coli, a double knockout of greA and greB did not show lethality, although colonies were s...

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“…Therefore, special transcription regulators are needed to support mycobacterial growth and gene regulatory networks are very complicated. For example, the transcription factors CarD and RbpA which are absent in E. coli perform essential roles for mycobacterial growth by stabilizing RPo [21,22], and interaction between RbpA and SigB regulates PPK1 transcription in mycobacteria [23]. The speci city of Mtsp17 probably adapts to the unstable mycobacterial RPo.…”

Section: Discussionmentioning

confidence: 99%

Discovery of a role for the single START-domain protein Mtsp17 in transcriptional regulation

Zhou

Zhong

Wei³

et al. 2020

Preprint

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Background Tuberculosis caused by the pathogen Mycobacterium tuberculosis (MTB), remains a significant threat to global health. Elucidating the mechanism of essential MTB genes will provide a theoretical basis for drug exploitation. Gene mtsp17 is essential and conserved in the Mycobacterium genus. Although the structure of Mtsp17 exhibits as a typical steroidogenic acute regulatory protein-related lipid transfer (START) family protein, its biological function is different from other START proteins. This study characterized the transcriptomes of Mycobacterium smegmatis to address the problem how suppressing mtsp17 reduces bacterial growth rate. Results 3% down- and 1% up-regulated protein-coding genes were significantly differentiated expressed by suppressing mtsp17 gene. Among them, desA1, an essential gene involved in mycolic acid synthesis, was found to be significantly depressed (3.1-fold). Further analyses showed that mstp17 can activate desA1 to regulate the bacterial growth. In addition, the anti-anti-SigF gene was dramatically decreased (8.9-fold) and 70 of the 79 differentially expressed genes showed the same change trends in the SigF knockout strain. The data indicate that Mtsp17 regulates SigF regulon by modulating mRNA abundance of the anti-sigma factor antagonist. Conclusions Our findings discover the role of Mtsp17 in transcriptional regulation that was unknown before, which provides new insights into the molecular mechanisms of START family and introduces a new node to the regulatory network of mycobacteria.

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CarD contributes to diverse gene expression outcomes throughout the genome of Mycobacterium tuberculosis

Cited by 35 publications

References 49 publications

The conserved transcriptional regulator CdnL is required for metabolic homeostasis and morphogenesis in Caulobacter

The conserved transcriptional regulator CdnL is required for metabolic homeostasis and morphogenesis in Caulobacter

Conditional down-regulation of GreA impacts expression of rRNA and transcription factors, affecting Mycobacterium smegmatis survival

Discovery of a role for the single START-domain protein Mtsp17 in transcriptional regulation

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