A Mathematical Model for Transcriptional Interference by RNA Polymerase Traffic in Escherichia coli

Sneppen, Kim; Dodd, Ian B.; Shearwin, Keith E.; Palmer, Adam C.; Schubert, Rachel A.; Callen, Benjamin P.; Egan, J. Barry

doi:10.1016/j.jmb.2004.11.075

Cited by 107 publications

(203 citation statements)

References 28 publications

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“…We found that interference with transcription from the weak pL promoter of coliphage 186 increases the further its distance from the convergent strong pR promoter [20]. Our modelling [47] confirms the expectation that TI caused by collisions should increase as the distance between two convergent promoters is increased and as their activity is increased. Natural examples of TI as a result of collision in genome networks are rare, with the convergent promoters pR and pRE of coliphage lambda being a possibility and thereby an inviting followup of the seminal study of Ward and Murray [61].…”

Section: Collisionssupporting

confidence: 85%

“…However, as with the development of molecular biology itself, studies in simple systems might provide direction. Mathematical modelling [47] is one approach to provide focus for future studies on the important parameters for each TI mechanism. Furthermore, examining the consequences of RNAP meeting a DNA-bound obstacle, such as Lac repressor [3] will provide vital clues for future studies that will help us understand what happens when an elongating RNAP meets a variety of DNA-bound obstacles, including, for example, a RNAP-like obstacle.…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of the 4462 known or predicted E. coli promoters in the RegulonDB database (v. 4) [46], reveals 166 non-overlapping tandem promoters pairs (with starts sites that are >70-bp apart) and 54 non-overlapping convergent promoter pairs with starts sites >40-bp and <200-bp apart [47]. In addition, there are 54 convergent, 89 divergent and 292 tandem promoters whose start sites are separated by <40 bp and so could be classified as overlapping promoters [25].…”

Section: How Widespread Is Transcriptional Interference?mentioning

confidence: 99%

“…Mathematical modelling [47] of TI indicates that sitting duck interference increases as the ratio of the strength of the aggressive to the sensitive promoter increases. Interference as a result of the sitting duck mechanism is maximal when the rate of formation of the initiation complex at the sensitive promoter is equal to its rate of firing.…”

Section: Sitting Duck Mechanismmentioning

confidence: 99%

“…Although their studies involved prokaryotic promoters, the concept could equally well apply in eukaryotic systems, should the transcribing RNA polymerase remove from the DNA either the initiation complex bound at the sensitive promoter or transcription factors associated with it. This is discussed in the following section.Mathematical modelling [47] of TI indicates that sitting duck interference increases as the ratio of the strength of the aggressive to the sensitive promoter increases. Interference as a result of the sitting duck mechanism is maximal when the rate of formation of the initiation complex at the sensitive promoter is equal to its rate of firing.…”

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confidence: 99%

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Transcriptional interference – a crash course

2005

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The term 'transcriptional interference' (TI) is widely used but poorly defined in the literature. There are a variety of methods by which one can interfere with the process or the product of transcription but the term TI usually refers to the direct negative impact of one transcriptional activity on a second transcriptional activity in cis. Two recent studies, one examining Saccharomyces cerevisiae and the other Escherichia coli, clearly show TI at one promoter caused by the arrival of a transcribing complex initiating at a distant promoter. TI is potentially widespread throughout biology; therefore, it is timely to assess exactly its nature, significance and operative mechanisms. In this article, we will address the following questions: what is TI, how important and widespread is it, how does it work and where should we focus our future research efforts? What is transcriptional interference?In this article, we wish to define transcriptional interference (TI) specifically as the suppressive influence of one transcriptional process, directly and in cis on a second transcriptional process. Our definition of TI (see Glossary) excludes the kind of interference that results from the following: (i) the binding of a repressor to its operator overlapping a promoter [1]; (ii) promoter modification, such as methylation [2]; (iii) hindering the progress of an elongating RNA polymerase (RNAP) by DNA-bound obstacles (other than a second RNAP) [3]; (iv) the inactivation of RNAP by RNA regulators [4]; (v) the insulation of an enhancer site [5]; and (vi) RNA interference (RNAi) in which the product of one transcriptional unit interferes with the half-life of the product of a second transcriptional unit [6]. We exclude from our definition of TI examples whereby transcription interferes directly with a cellular activity rather than with transcription associated with cellular activity (e.g. the interference with chromosome replication in Saccharomyces cerevisiae as a result of transcription across its site of initiation [7]). We also exclude those cases of 'negative interference' whereby one transcriptional process, directly and in cis, enhances rather than suppresses a second transcriptional process, such as the fortuitous positioning of a gene within an active chromatin domain [8], chromatin remodelling that promotes intergenic transcription [9] and transcriptional coupling in which a promoter is activated by the activity of an upstream divergent promoter [10].TI is often asymmetric and results from the existence of two promoters, the strong (aggressive) promoter reducing the expression of the weak (sensitive) promoter (Figure 1). These promoters can be either: (i) convergent promoters directing converging transcripts that overlap for at least part of their sequence ( Figure 1a); (ii) tandem promoters, one upstream of the other but transcribing in the same direction, with their transcripts possibly but not necessarily overlapping ( Figure 1b); or (iii) overlapping promoters, either divergent, convergent or tandem, in whi...

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Section: Collisionssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: How Widespread Is Transcriptional Interference?mentioning

confidence: 99%

Section: Sitting Duck Mechanismmentioning

confidence: 99%

mentioning

confidence: 99%

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Transcriptional interference – a crash course

2005

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RNA polymerase pausing at a protein roadblock can enhance transcriptional interference by promoter occlusion

et al. 2019

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Convergent promoters exert transcriptional interference ( TI ) by several mechanisms including promoter occlusion, where elongating RNA polymerases ( RNAP s) block access to a promoter. Here, we tested whether pausing of RNAP s by obstructive DNA ‐bound proteins can enhance TI by promoter occlusion. Using the Lac repressor as a ‘roadblock’ to induce pausing over a target promoter, we found only a small increase in TI , with mathematical modelling suggesting that rapid termination of the stalled RNAP was limiting the occlusion effect. As predicted, the roadblock‐enhanced occlusion was significantly increased in the absence of the Mfd terminator protein. Thus, protein roadblocking of RNAP may cause pause‐enhanced occlusion throughout genomes, and the removal of stalled RNAP may be needed to minimize unwanted TI .

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Phenotypic noise: effects of post‐transcriptional regulatory processes affecting mRNA

2013

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The inherently stochastic nature of biomolecular processes is one of the main sources giving rise to cell-to-cell variations in protein and mRNA abundance, termed noise. Noise in isogenic populations can enhance survival under adverse conditions and stress, and has therefore played a fundamental role in evolution. On the other hand, noise may have detrimental effects and therefore cells must also display robustness to fluctuations and possess mechanisms of control in order to function properly. Noise can be introduced at every step in the cascade of intermediate events resulting in the production of functional proteins. While initial studies of noise focused on stochasticity introduced at the transcriptional level, recent years have witnessed a gradual shift of emphasis into the effects that post-transcriptional processes have on phenotypic noise. Here, we survey the insights that have been gained on the effects of processes that modify RNA transcript populations on phenotypic noise, including regulation by noncoding RNAs in prokaryotes and eukaryotes, alternative splicing and transcriptional interference.

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A Mathematical Model for Transcriptional Interference by RNA Polymerase Traffic in Escherichia coli

Cited by 107 publications

References 28 publications

Transcriptional interference – a crash course

Transcriptional interference – a crash course

RNA polymerase pausing at a protein roadblock can enhance transcriptional interference by promoter occlusion

Phenotypic noise: effects of post‐transcriptional regulatory processes affecting mRNA

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