The evolving story of the omega subunit of bacterial RNA polymerase

Mathew, Renjith; Chatterji, Dipankar

doi:10.1016/j.tim.2006.08.002

Cited by 70 publications

(69 citation statements)

References 59 publications

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“…The ω subunit is one of the universally conserved core subunits present in all cellular RNAPs (36), but its functions remain only partially understood (37). We provide the first evidence, to our knowledge, that ω is involved in the regulation of transcription elongation and termination.…”

Section: Discussionmentioning

confidence: 82%

Distinct pathways of RNA polymerase regulation by a phage-encoded factor

Esyunina

Klimuk

Severinov

et al. 2015

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

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Transcription antitermination is a common strategy of gene expression regulation, but only a few transcription antitermination factors have been studied in detail. Here, we dissect the transcription antitermination mechanism of Xanthomonas oryzae virus Xp10 protein p7, which binds host RNA polymerase (RNAP) and regulates both transcription initiation and termination. We show that p7 suppresses intrinsic termination by decreasing RNAP pausing and increasing the transcription complex stability, in cooperation with host-encoded factor NusA. Uniquely, the antitermination activity of p7 depends on the ω subunit of the RNAP core and is modulated by ppGpp. In contrast, the inhibition of transcription initiation by p7 does not require ω but depends on other RNAP sites. Our results suggest that p7, a bifunctional transcription factor, uses distinct mechanisms to control different steps of transcription. We propose that regulatory functions of the ω subunit revealed by our analysis may extend to its homologs in eukaryotic RNAPs.RNA polymerase | transcription antitermination | transcription pausing | omega subunit | NusA T ranscription promoters and terminators are the main "punctuation marks" that control the expression of individual genes in the genome. In bacteria, transcription termination is an essential regulatory step that determines the relative levels of expression of promoter-proximal and distal genes within operons. Depending on the factors involved, transcription termination in bacteria can be classified as intrinsic (depends on RNAencoded signals) or factor-dependent (requires additional protein factors such as Rho helicase). Intrinsic terminators consist of a G/C-rich hairpin formed in the nascent RNA followed by a downstream oligo(U) tract. During intrinsic termination, RNA polymerase (RNAP) pauses after synthesizing an oligo(U) sequence, accompanied by hairpin formation, leading to subsequent dissociation of the transcription elongation complex (TEC) (1, 2). Despite the relatively simple overall scenario, the exact mechanisms of pausing and hairpin-induced TEC destabilization remain an issue of debate (1, 3).Transcription antitermination is a widespread phenomenon involved in regulation of bacterial and phage operons (2). Transcription antitermination is often mediated by specialized protein factors that target host RNAP and can suppress termination at multiple sites in the operon. The well-studied examples of phage antiterminators include proteins N and Q of Escherichia coli phage λ and the gp39 protein of Thermus thermophilus phage P23-45. These factors suppress RNAP pausing, thus inhibiting the first step of the termination pathway (4-6). The antitermination activity of N and Q, but not gp39, is enhanced by cell-encoded proteins, including transcription elongation factor NusA, which by itself stimulates termination but reverses its activity to additionally stabilize the TEC in cooperation with N and Q (5, 6). Curiously, the N, Q, gp39, and NusA proteins all target the flexible β flap domain of RNAP (2, 4...

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Section: Discussionmentioning

confidence: 82%

Distinct pathways of RNA polymerase regulation by a phage-encoded factor

Esyunina

Klimuk

Severinov

et al. 2015

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

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“…Functionally, the subunit is the least understood subunit, but there is a clear link between the subunit and ppGpp-dependent transcription (45,46). The finding that the subunit structure is so different in the E. coli and Thermus RNAPs may be related to the observation that E. coli RNAP can respond to ppGpp only in the presence of the subunit (46,47).…”

Section: Structural Comparison Of E Coli and Thermus Rnaps-the Strucmentioning

confidence: 99%

X-ray Crystal Structure of Escherichia coli RNA Polymerase σ70 Holoenzyme

Murakami

2013

Journal of Biological Chemistry

184

221

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Background: A crystal structure of Escherichia coli RNA polymerase (RNAP) has not been determined. Results: The 1.1 and ␣ subunit C-terminal domain structures have been determined in the context of an intact RNAP. Conclusion: 1.1 localizes within the RNAP DNA-binding channel and must disengage from this site to form an open complex. Significance: This work enables future structure determination of bacterial RNAP mutants.

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“…While it is well studied in Gram-negative bacteria (10) and eukaryotes (9), a recent review by our group highlighted the need for to be examined in a wider range of species, and particularly Gram-positive bacteria (6). This is especially true since (i) the subunit has a variety of possible roles that have received only limited attention in Gram-positive species, including RNAP subunit folding (9, 12, 13, 15) and stability (16), complex assembly/stabilization (10,13,14), maintenance of factor specificity (24,25), and ppGpp binding (19)(20)(21), and (ii) Gram-positive species, and particularly the Firmicutes, include several epidemiologically relevant human pathogens. To the latter point, an understanding of cellular factors that are required for transcription and to maintain transcriptional stringency is crucial in order to better comprehend the physiology of pathogens and thus potentially aid in counteracting and preventing the spread of disease.…”

Section: Discussionmentioning

confidence: 99%

“…While the presence of these two subunits is largely confined to the Firmicutes, homologs of , the smallest of the three subunits, can be found not only in bacteria but also in eukaryotes (RPB6) and archaea (RpoK) (6,9). Although this conservation might suggest a vital role and perhaps similar function across widely different species, there are in fact marked differences in how this subunit influences cells across the various kingdoms (6,10). Most strikingly is the observation that while it is accessory in bacteria, the subunit is essential in eukaryotic organisms (11).…”

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The ω Subunit Governs RNA Polymerase Stability and Transcriptional Specificity in Staphylococcus aureus

et al. 2017

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Staphylococcus aureus is a major human pathogen that causes infection in a wide variety of sites within the human body. Its ability to adapt to the human host and to produce a successful infection requires precise orchestration of gene expression. While DNA-dependent RNA polymerase (RNAP) is generally well characterized, the roles of several small accessory subunits within the complex have yet to be fully explored. This is particularly true for the omega ( or RpoZ) subunit, which has been extensively studied in Gram-negative bacteria but largely neglected in Grampositive counterparts. In Escherichia coli, it has been shown that ppGpp binding, and thus control of the stringent response, is facilitated by . Interestingly, key residues that facilitate ppGpp binding by are not conserved in S. aureus, and consequently, survival under starvation conditions is unaffected by rpoZ deletion. Further to this, -lacking strains of S. aureus display structural changes in the RNAP complex, which result from increased degradation and misfolding of the ␤= subunit, alterations in ␦ and factor abundance, and a general dissociation of RNAP in the absence of . Through RNA sequencing analysis we detected a variety of transcriptional changes in the rpoZ-deficient strain, presumably as a response to the negative effects of depletion on the transcription machinery. These transcriptional changes translated to an impaired ability of the rpoZ mutant to resist stress and to fully form a biofilm. Collectively, our data underline, for the first time, the importance of for RNAP stability, function, and cellular physiology in S. aureus. IMPORTANCEIn order for bacteria to adjust to changing environments, such as within the host, the transcriptional process must be tightly controlled. Transcription is carried out by DNA-dependent RNA polymerase (RNAP). In addition to its major subunits (␣ 2 ␤␤=) a fifth, smaller subunit, , is present in all forms of life. Although this small subunit is well studied in eukaryotes and Gram-negative bacteria, only limited information is available for Gram-positive and pathogenic species. In this study, we investigated the structural and functional importance of , revealing key roles in subunit folding/stability, complex assembly, and maintenance of transcriptional integrity. Collectively, our data underline, for the first time, the importance of for RNAP function and cellular harmony in S. aureus.KEYWORDS RNA polymerase subunit omega, RpoZ, Staphylococcus aureus, gene regulation T ranscription in all forms of life is a tightly controlled process, necessitated by the essentiality of correct temporal and spatial expression of genes for survival. All transcriptional activity within a cell is maintained by the DNA-dependent RNA polymerase (RNAP). This multiprotein complex is structurally and functionally similar in distant forms of life, displaying only minor variations in composition, e.g., the presence/ absence of certain subunits (1, 2). In bacteria RNAP consists of four main subunits, i.e.,

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The evolving story of the omega subunit of bacterial RNA polymerase

Cited by 70 publications

References 59 publications

Distinct pathways of RNA polymerase regulation by a phage-encoded factor

Distinct pathways of RNA polymerase regulation by a phage-encoded factor

X-ray Crystal Structure of Escherichia coli RNA Polymerase σ70 Holoenzyme

The ω Subunit Governs RNA Polymerase Stability and Transcriptional Specificity in Staphylococcus aureus

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