NusG-Spt5 Proteins—Universal Tools for Transcription Modification and Communication

Tomar, Sushil Kumar; Artsimovitch, Irina

doi:10.1021/cr400064k

Cited by 57 publications

(62 citation statements)

References 196 publications

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“…NusG is a universally conserved transcription factor in prokaryotes. In E. coli, it was shown to be indispensable for termination of transcription governed by Rho (reviewed by Tomar & Artsimovitch, 2013). E. coli NusG physically couples transcription and translation as it binds to RNAP, and concurrently, either Rho or NusE -a ribosomal S10 protein (Burmann et al, 2010).…”

Section: Suppression Of Pervasive Transcriptionmentioning

confidence: 99%

Transcription termination factor Rho: a hub linking diverse physiological processes in bacteria

et al. 2016

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Factor-dependent termination of transcription in bacteria relies on the activity of a specific RNA helicase, the termination factor Rho. Rho is nearly ubiquitous in bacteria, but the extent to which its physiological functions are conserved throughout the different phyla remains unknown. Most of our current knowledge concerning the mechanism of Rho's activity and its physiological roles comes from the model micro-organism Escherichia coli, where Rho is essential and involved in the control of several important biological processes. However, the rather comprehensive knowledge about the general mechanisms of action and activities of Rho based on the E. coli paradigm cannot be directly extrapolated to other bacteria. Recent studies performed in different species favour the view that Rho-dependent termination plays a significant role even in bacteria where Rho is not essential. Here, we summarize the current state of the ever-increasing knowledge about the various aspects of the physiological functions of Rho, such as limitation of deleterious foreign DNA expression, control of gene expression, suppression of pervasive transcription, prevention of R-loops and maintenance of chromosome integrity, focusing on similarities and differences of the activities of Rho in various bacterial species. Introduction Transcription termination is a critical step in gene regulation in all living organisms. In bacteria, transcription termination is well known to be essential for the generation of different types of functional RNAs, the definition of the boundaries of the transcriptional units, the release of RNA polymerase (RNAP) and the regulation of gene expression via the mechanism known as transcription attenuation (Peters et al., 2011;Santangelo & Artsimovitch, 2011).However, recent studies have revealed new roles of transcriptional termination, e.g. those linked to the maintenance of genome integrity or degradation of untranslated mRNAs. Particular attention is now paid to transcription termination due to its crucial role in the control of pervasive transcription. This type of genome-wide transcription, not associated with annotated genome features such as protein-coding genes, is a universal phenomenon for all the three domains of life and viruses (Georg & Hess, 2011;Wade & Grainger, 2014). In eukaryotes, pervasive transcription arises mainly from bidirectional promoters that synthesize both mRNA and diverse non-coding RNAs, but this phenomenon is also controlled by selective transcriptional termination (Kapranov et al., 2007;Schulz et al., 2013). Recently, an essential role of transcription termination in the control of pervasive transcription was demonstrated for both Gram-positive and Gram-negative model micro-organisms Bacillus subtilis and Escherichia coli (Nicolas et al., 2012;Peters et al., 2012).In bacteria, transcription termination is achieved by two mechanisms: factor-independent (intrinsic) and factordependent termination. Intrinsic termination is strongly associated with sequence-specific signals characterized by ...

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Section: Suppression Of Pervasive Transcriptionmentioning

confidence: 99%

Transcription termination factor Rho: a hub linking diverse physiological processes in bacteria

et al. 2016

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“…It is possible that the affinity of the KOW domain for RNA leads to nonspecific interactions with the emerging transcript; however, it is tempting to speculate about greater involvement of the KOW domain based on the known activities of the C terminus of bacterial NusG (108). Bacterial NusG can facilitate elongation or termination depending on its binding partner (99)(100)(101)(109)(110)(111).…”

Section: Transcription Factor Spt5mentioning

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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“…1C), which might induce pausing instead of antipausing to the EC. RfaH, a NusG family protein, has similar NTD conformations as NusG and interacts at the similar site(s) of the EC, but induces pausing at specific sites called the ops sites (7). It is alluring to suggest that Rho-NusG CTD interactions allosterically exert shuttle conformational changes to the NusG-NTD so that the latter behaves functionally similar to RfaH-NTD, and induces enhanced pauses at the Rho-termination sites.…”

Section: Figure 9 Functional Interaction Sites Of Nusg On the Rho Hementioning

confidence: 99%

“…NusG, a transcription elongation factor, being bound to the elongation complex (EC) through its N-terminal domain (NTD) helps the latter to overcome the pauses by increasing the elongation rate (5,7,8). Its C-terminal domain (CTD) is capable of interacting with the Rho (9).…”

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confidence: 99%

Molecular Basis of NusG-mediated Regulation of Rho-dependent Transcription Termination in Bacteria

Valabhoju

Agrawal

Sen

2016

Journal of Biological Chemistry

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The bacterial transcription elongation factor NusG stimulates the Rho-dependent transcription termination through a direct interaction with Rho. The mechanistic basis of NusG dependence of the Rho function is not known. Here, we describe Rho* mutants I168V, R221C/A, and P235H that do not require NusG for their termination function. These Rho* mutants have acquired new properties, which otherwise would have been imparted by NusG. A detailed analyses revealed that they have more stable interactions at the secondary RNA binding sites of Rho, which reduced the lag in initiating its ATPase as well as the translocase activities. These more stable interactions arose from the significant spatial re-orientations of the P, Q, and R structural loops of the Rho central channel. We propose that NusG imparts similar conformational changes in the central channel of Rho, yielding faster isomerization of the open to the closed hexameric states of the latter during its RNA-loading step. This acceleration stabilizes the Rho-RNA interactions at many terminators having suboptimal rut sites, thus making Rho-NusG interactions so essential in vivo. Finally, identification of the NusG binding sites on the Rho hexamer led us to conclude that the former exerts its effect allosterically.At the end of a significant number of operons in Escherichia coli, DNA sequences do not code for intrinsic termination signals, characterized by a hairpin and a U-stretch (1). Transcription termination factor Rho, a homo-hexameric RNA-dependent ATPase, induces termination in these operons. Rho loads onto unstructured C-rich RNA sequences (rut sites, the Rhoutilization sites) and is capable of translocating along the RNA using its RNA-dependent ATPase activity, and eventually dislodges the elongating RNA polymerase (RNAP) 3 (1, 2). By virtue of these properties of Rho, long stretches of untranslated RNA sequences are its ideal targets. Transcription on these stretches can face premature termination by Rho, which usually happens in the cases of transcription-translation uncoupling. Recent genomics study has revealed that Rho-dependent termination is widespread in vivo, which could be the main reason for its essentiality (3-6).NusG, a transcription elongation factor, being bound to the elongation complex (EC) through its N-terminal domain (NTD) helps the latter to overcome the pauses by increasing the elongation rate (5, 7, 8). Its C-terminal domain (CTD) is capable of interacting with the Rho (9). This interaction stimulates the Rho-dependent termination process in vitro, which is manifested as early termination (10, 11). More recent studies indicated that NusG is essential for recruiting Rho on a subset of terminators in vivo (4, 6). Mechanism of stimulation of Rho-dependent termination by NusG in vitro as well as the molecular basis of NusG dependence of Rho to utilize a subset of terminators in vivo is not known, knowledge of which is essential to understand the intricacies of this transcription termination process.In this study, by screening a library of ...

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NusG-Spt5 Proteins—Universal Tools for Transcription Modification and Communication

Cited by 57 publications

References 196 publications

Transcription termination factor Rho: a hub linking diverse physiological processes in bacteria

Transcription termination factor Rho: a hub linking diverse physiological processes in bacteria

Transcription Regulation in Archaea

Molecular Basis of NusG-mediated Regulation of Rho-dependent Transcription Termination in Bacteria

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