ATP-dependent motor activity of the transcription termination factor Rho from<i>Mycobacterium tuberculosis</i>

D’Heygere, F; Schwartz, Annie; Coste, Franck; Castaing, B.; Boudvillain, Marc

doi:10.1093/nar/gkv505

Cited by 29 publications

(68 citation statements)

References 56 publications

(144 reference statements)

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“…It was hypothesized that the N-terminal domain might be responsible for the apparent dispensability of ATP hydrolysis. In contrast, a second study found ATP hydrolysis to be essential for transcription termination by M. tuberculosis Rho in vitro 26. To evaluate importance of ATP binding to Rho for growth of M. tuberculosis we mutated the amino acids D440, R541 and E386 to N440, A541 and A386.…”

Section: Resultsmentioning

confidence: 99%

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Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death

et al. 2017

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Rifampicin, which inhibits bacterial RNA polymerase, provides one of the most effective treatments for tuberculosis. Inhibition of the transcription termination factor Rho is used to treat some bacterial infections, but its importance varies across bacteria. Here we show that Rho of Mycobacterium tuberculosis functions to both define the 3′ ends of mRNAs and silence substantial fragments of the genome. Brief inactivation of Rho affects over 500 transcripts enriched for genes of foreign DNA elements and bacterial virulence factors. Prolonged inactivation of Rho causes extensive pervasive transcription, a genome-wide increase in antisense transcripts, and a rapid loss of viability of replicating and non-replicating M. tuberculosis in vitro and during acute and chronic infection in mice. Collectively, these data suggest that inhibition of Rho may provide an alternative strategy to treat tuberculosis with an efficacy similar to inhibition of RNA polymerase.

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Section: Resultsmentioning

confidence: 99%

“…Interestingly, Rho of M. tuberculosis is predicted to be essential for growth2425, but is poorly inhibited by BCM (ref. 26), which suggests that targeting mycobacterial Rho could allow development of genus-specific antibiotics.…”

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confidence: 99%

Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death

et al. 2017

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“…Critical, direct molecular interactions between Spt5 and RNAP have been identified in both Bacteria and Archaea, and the conservation of RNAP and Spt5 infers that these same interactions are used in Eukarya. Briefly, a hydrophobic depression on the NGN domain interacts with the mobile clamp domain of RNAP, with additional interactions between the NGN domain and RNAP jaw domain likely fixing the location of the clamp domain in a closed configuration (81). Spt5 interaction with RNAP is not necessary for productive and processive elongation in vitro, but the interaction does increase the total output of transcription systems (1).…”

Section: Regulation Of Transcription Elongationmentioning

confidence: 99%

Factor-dependent archaeal transcription termination

Walker

Luyties

Santangelo

2017

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

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We demonstrate that binding of the conserved and essential archaeal transcription factor TFE to the archaeal RNAP is directed, in part, by interactions with the RpoE subunit of RNAP. As the surfaces involved are conserved in many eukaryotic and archaeal systems, the identified TFE-RNAP interactions are likely conserved in archaeal-eukaryal systems and represent an important point of contact that can influence the efficiency of transcription initiation.While many studies in archaea have focused on elucidating the mechanism of transcription initiation and elongation, studies on termination were slower to emerge.Transcription factors promoting initiation and elongation have been characterized in each Domain but transcription termination factors have only been identified in bacteria and eukarya.Here we characterize the first archaeal termination factor (termed Eta) capable of disrupting the transcription elongation complex, detail the rate of and requirements for Eta-mediated transcription termination and describe a role for Eta in transcription termination in vivo. Etamediated transcription termination is energy-dependent, requires upstream DNA sequences and disrupts transcription elongation complexes to release the nascent RNA to solution. Deletion of TK0566 (encoding Eta) is possible, but results in slow growth and renders cells sensitive to iii DNA damaging agents. Structure-function studies reveal that the N-terminal domain of Eta is not necessary for Eta-mediated termination in vitro, but Thermococcus kodakarensis cells lacking the N-terminal domain exhibit slow growth compared to parental strains. We report the first crystal structure of Eta that will undoubtedly lead to further structure-function analyses. The results obtained argue that the mechanisms employed by termination factors in archaea, eukarya, and bacteria to disrupt the transcription elongation complex may be conserved and that Eta stimulates release of stalled or arrested transcription elongation complexes.iv ACKNOWLEDGEMENTS

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“…Transcription is highly regulated, and the transcription cycle is typically demarcated into three phases: initiation, elongation, and termination (9)(10)(11)(12)(13) (Fig. 1).…”

Section: The Archaeal Transcription Cyclementioning

confidence: 99%

“…Bioinformatic analyses reveal some potential targets that remain to be more fully evaluated, but there are no easily identified homologues of known eukaryotic or bacterial termination factors. Two well-studied transcription bacterial termination factors, Rho and Mfd (13,(146)(147)(148)(149)(150), lack clear homologues in archaeal genomes, but there are hints that analogous activities may be present in archaeal species. Rho is a homohexamer helicase that represses phage transcription and mediates polar repression of downstream genes when transcription and translation become uncoupled (142,(151)(152)(153).…”

Section: Identification Of Factor-dependent Terminationmentioning

confidence: 99%

Transcription Regulation in Archaea

2016

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The known diversity of metabolic strategies and physiological adaptations of archaeal species to extreme environments is extraordinary. Accurate and responsive mechanisms to ensure that gene expression patterns match the needs of the cell necessitate regulatory strategies that control the activities and output of the archaeal transcription apparatus. Archaea are reliant on a single RNA polymerase for all transcription, and many of the known regulatory mechanisms employed for archaeal transcription mimic strategies also employed for eukaryotic and bacterial species. Novel mechanisms of transcription regulation have become apparent by increasingly sophisticated in vivo and in vitro investigations of archaeal species. This review emphasizes recent progress in understanding archaeal transcription regulatory mechanisms and highlights insights gained from studies of the influence of archaeal chromatin on transcription. RNA polymerase (RNAP) is a well-conserved, multisubunit essential enzyme that transcribes DNA to generate RNA in all cells. Although RNA synthesis is carried out by RNAP, the activities of RNAP during each phase of transcription are subject to basal and regulatory transcription factors. Substantial differences in transcription regulatory strategies exist in the three domains (Bacteria, Archaea, and Eukarya). Only a single transcription factor (NusG or Spt5) is universally conserved (1, 2), and the roles of many archaeon-encoded factors have not been evaluated using in vivo and in vitro techniques. Archaea are reliant on a transcription apparatus that is homologous to the eukaryotic transcription machinery; similarities include additional RNAP subunits that form a discrete subdomain of RNAP (3, 4) as well as basal transcription factors that direct transcription initiation and elongation (5-8).The shared homology of archaeal-eukaryotic transcription components aligns with the shared ancestry of Archaea and Eukarya, and this homology often is exclusive of Bacteria. Archaea are prokaryotic, but the transcription apparatus of Bacteria differs significantly from that of Archaea and Eukarya.The archaeal transcription apparatus is most commonly summarized as a simplified version of the eukaryotic machinery. In some respects this is true, as homologs of only a few eukaryotic transcription factors are encoded in archaeal genomes, and archaeal transcription in vitro can be supported by just a few transcription factors. However, much regulatory activity in eukaryotes is devoted to posttranslational modifications of chromatin, RNAP, and transcription factors, and this complexity seemingly does not transfer to the Archaea, where few posttranslational modifications or chromatin-imposed regulation events are currently known. The ostensible simplicity of archaeal transcription is under constant revision, as more detailed examinations of archaeon-encoded factors become possible through increasingly sophisticated in vivo and in vitro techniques. This review will highlight the current understanding of archaeal transcriptio...

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ATP-dependent motor activity of the transcription termination factor Rho fromMycobacterium tuberculosis

Cited by 29 publications

References 56 publications

Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death

Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death

Factor-dependent archaeal transcription termination

Transcription Regulation in Archaea

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