TraR, a Homolog of a RNAP Secondary Channel Interactor, Modulates Transcription

Blankschien, Matthew D.; Potrykus, Katarzyna; Grace, Elicia D.; Choudhary, Abha; Vinella, Daniel; Cashel, Michael; Herman, Christophe

doi:10.1371/journal.pgen.1000345

Cited by 48 publications

(93 citation statements)

References 58 publications

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“…Accordingly, other factors likely influence regulation by ppGpp 0 and dksA mutant cells. For example, TraR upregulates transcription from amino acid promoters and downregulates transcription from ribosomal promoters in the absence of ppGpp and DksA (22). Therefore, additional work is required before these complex regulatory interactions are fully understood.…”

Section: Regulatory Targets Of Ppgppmentioning

confidence: 99%

“…However, TraR functions in the absence of ppGpp (22). An understanding of how TraR acts independently of ppGpp will likely provide clues to the mechanisms of ppGpp-and DksA-dependent transcriptional control.…”

Section: Uropathogenic Escherichia Colimentioning

confidence: 99%

“…An understanding of how TraR acts independently of ppGpp will likely provide clues to the mechanisms of ppGpp-and DksA-dependent transcriptional control. Its self-sufficiency and presence on a conjugative plasmid, together with the general propensity of bacteria to integrate ppGpp into the regulation of pathogenicity island genes, make TraR, like other DksA homologues, a candidate activator of specialized bacterial virulence systems (22).…”

Section: Uropathogenic Escherichia Colimentioning

confidence: 99%

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ppGpp Conjures Bacterial Virulence

Dalebroux

Svensson

Gaynor

et al. 2010

Microbiol Mol Biol Rev

333

364

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SUMMARY Like for all microbes, the goal of every pathogen is to survive and replicate. However, to overcome the formidable defenses of their hosts, pathogens are also endowed with traits commonly associated with virulence, such as surface attachment, cell or tissue invasion, and transmission. Numerous pathogens couple their specific virulence pathways with more general adaptations, like stress resistance, by integrating dedicated regulators with global signaling networks. In particular, many of nature's most dreaded bacteria rely on nucleotide alarmones to cue metabolic disturbances and coordinate survival and virulence programs. Here we discuss how components of the stringent response contribute to the virulence of a wide variety of pathogenic bacteria.

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Section: Regulatory Targets Of Ppgppmentioning

confidence: 99%

Section: Uropathogenic Escherichia Colimentioning

confidence: 99%

Section: Uropathogenic Escherichia Colimentioning

confidence: 99%

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ppGpp Conjures Bacterial Virulence

Dalebroux

Svensson

Gaynor

et al. 2010

Microbiol Mol Biol Rev

333

364

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“…71). DksA, like the plasmid-encoded quorum sensing regulator (TraR) protein (72), inhibits ribosomal protein promoters and rrn initiation (73,74) and is more distant from OriC than is greA. In vivo it would act to reduce the rate of rrn initiation and hence antagonize transcription foci formation.…”

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confidence: 99%

Gene order and chromosome dynamics coordinate spatiotemporal gene expression during the bacterial growth cycle

Sobetzko

Travers²,

Muskhelishvili³

2011

Proc. Natl. Acad. Sci. U.S.A.

203

261

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In Escherichia coli crosstalk between DNA supercoiling, nucleoid-associated proteins and major RNA polymerase σ initiation factors regulates growth phase-dependent gene transcription. We show that the highly conserved spatial ordering of relevant genes along the chromosomal replichores largely corresponds both to their temporal expression patterns during growth and to an inferred gradient of DNA superhelical density from the origin to the terminus. Genes implicated in similar functions are related mainly in trans across the chromosomal replichores, whereas DNA-binding transcriptional regulators interact predominantly with targets in cis along the replichores. We also demonstrate that macrodomains (the individual structural partitions of the chromosome) are regulated differently. We infer that spatial and temporal variation of DNA superhelicity during the growth cycle coordinates oxygen and nutrient availability with global chromosome structure, thus providing a mechanistic insight into how the organization of a complete bacterial chromosome encodes a spatiotemporal program integrating DNA replication and global gene expression. In Escherichia coli cells the physiological transitions induced by the changing growth environment are accompanied by changes in DNA superhelical density (1-3), nucleoid structure (4-6), and the promoter selectivity of the RNA polymerase (RNAP) holoenzyme (3, 7). During the growth cycle both the relative and absolute concentrations of the abundant nucleoid-associated proteins (NAPs ; Table S1) change substantially and correspondingly generate bacterial chromatin of variable composition (8, 9). The NAPs stabilize distinct supercoil structures (10-12) selectively favoring particular RNAP holoenzymes (13-15). These variable nucleoprotein complexes modulate DNA topology during the growth cycle (Fig. 1A), optimizing the channeling of supercoil energy into appropriate metabolic pathways (16,17).The expression of the genes determining superhelical density, polymerase selectivity, and nucleoid structure is coordinated by cross-regulation. Thus, factor for inversion stimulation (FIS), a NAP abundant during the early exponential phase (18), regulates expression not only of the superhelicity determinants DNA gyrase subunits A and B (gyrA and gyrB) and topoisomerase I (topA) (19-21) but also other NAP-encoding genes including hns, α subunit of histone-like protein from E. coli strain U93 (hupA), and DNA binding protein from starved cells (dps) (22-24) and components of the transcription machinery such as σ 38 subunit of RNA polymerase rpoS (25). Similarly mutations affecting the selectivity of RNAP influence NAP production (26-28). Again, mutations in the genes controlling DNA superhelicity affect the production of both NAPs and the basal transcription machinery (27,29). This pattern of integrated control constitutes a heterarchical network coordinating chromosome structure with cellular metabolism (27,28,30). A further pointer to this integrated network is the observed selection of mutations in fis...

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“…The name GreA was derived from its apparent ability to regulate growth (growth regulator). Currently, a large and still growing structural family of secondary channel proteins (GreA, GreB, DksA, RfaH, TraR, Gfh1, and eukaryotic TFIIS) are thought to interact with this RNAP channel for entry of substrates into the catalytic site and for extrusion of backtracked nascent RNA (6,7,13,21,31,47). The functions of these proteins are different despite similar structures.…”

mentioning

confidence: 99%

Effects on Growth by Changes of the Balance between GreA, GreB, and DksA Suggest Mutual Competition and Functional Redundancy in Escherichia coli

et al. 2012

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It is well known that ppGpp and DksA interact with bacterial RNA polymerase (RNAP) to alter promoter activity. This study suggests that GreA plays a major role and GreB plays a minor role in the ppGpp-DksA regulatory network. We present evidence that DksA and GreA/GreB are redundant and/or share similar functions: (i) on minimal medium GreA overproduction suppresses the growth defects of a dksA mutant; (ii) GreA and DksA overexpression partially suppresses the auxotrophy of a ppGppdeficient strain; (iii) microarrays show that many genes are regulated similarly by GreA and DksA. We also find instances where GreA and DksA seem to act in opposition: (i) complete suppression of auxotrophy occurs by overexpression of GreA or DksA only in the absence of the other protein; (ii) PgadA and PgadE promoter fusions, along with many other genes, are dramatically affected in vivo by GreA overproduction only when DksA is absent; (iii) GreA and DksA show opposite regulation of a subset of genes. Mutations in key acidic residues of GreA and DksA suggest that properties seen here probably are not explained by known biochemical activities of these proteins. Our results indicate that the general pattern of gene expression and, in turn, the ability of Escherichia coli to grow under a defined condition are the result of a complex interplay between GreA, GreB, and DksA that also involves mutual control of their gene expression, competition for RNA polymerase binding, and similar or opposite action on RNA polymerase activity.

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TraR, a Homolog of a RNAP Secondary Channel Interactor, Modulates Transcription

Cited by 48 publications

References 58 publications

ppGpp Conjures Bacterial Virulence

ppGpp Conjures Bacterial Virulence

Gene order and chromosome dynamics coordinate spatiotemporal gene expression during the bacterial growth cycle

Effects on Growth by Changes of the Balance between GreA, GreB, and DksA Suggest Mutual Competition and Functional Redundancy in Escherichia coli

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