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Effects of transcriptional pausing on gene expression dynamics.

Rajala T, Häkkinen A, Healy S, Yli-Harja O, Ribeiro AS - PLoS Comput. Biol. (2010)

Bottom Line: We show that pauses' duration and rate of occurrence affect the bursting in RNA production, transcriptional and translational noise, and the transient to reach mean RNA and protein levels.In a genetic repressilator, increasing the pausing rate and the duration of pausing events increases the period length but does not affect the robustness of the periodicity.We conclude that RNA polymerase pausing might be an important evolvable feature of genetic networks.

View Article: PubMed Central - PubMed

Affiliation: Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, Tampere, Finland.

ABSTRACT
Stochasticity in gene expression affects many cellular processes and is a source of phenotypic diversity between genetically identical individuals. Events in elongation, particularly RNA polymerase pausing, are a source of this noise. Since the rate and duration of pausing are sequence-dependent, this regulatory mechanism of transcriptional dynamics is evolvable. The dependency of pause propensity on regulatory molecules makes pausing a response mechanism to external stress. Using a delayed stochastic model of bacterial transcription at the single nucleotide level that includes the promoter open complex formation, pausing, arrest, misincorporation and editing, pyrophosphorolysis, and premature termination, we investigate how RNA polymerase pausing affects a gene's transcriptional dynamics and gene networks. We show that pauses' duration and rate of occurrence affect the bursting in RNA production, transcriptional and translational noise, and the transient to reach mean RNA and protein levels. In a genetic repressilator, increasing the pausing rate and the duration of pausing events increases the period length but does not affect the robustness of the periodicity. We conclude that RNA polymerase pausing might be an important evolvable feature of genetic networks.

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Related in: MedlinePlus

Effects of a sequence-specific long-duration pause.Time interval between the completion of consecutive RNA molecules in a gene with 400 nucleotides in case (A) without long-duration pause sites, case (B) with one long-pause site at nucleotide 200 where kpause is half the value of the rate of stepwise elongation and dpause is 1 min, and case (C), identical to case (B) but with a 20% chance that a long-paused RNAP will lead to premature termination.
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pcbi-1000704-g009: Effects of a sequence-specific long-duration pause.Time interval between the completion of consecutive RNA molecules in a gene with 400 nucleotides in case (A) without long-duration pause sites, case (B) with one long-pause site at nucleotide 200 where kpause is half the value of the rate of stepwise elongation and dpause is 1 min, and case (C), identical to case (B) but with a 20% chance that a long-paused RNAP will lead to premature termination.

Mentions: In Figure 9, the distribution of time intervals between transcription completion events in the three scenarios A, B, and C are shown. The effects of the probabilistic long-pauses and premature termination at nucleotide 200 are visible comparing the figures. We set a high transcription initiation rate so that, given the promoter open complex delay, transcription events are separated on average by 40±4 s intervals.


Effects of transcriptional pausing on gene expression dynamics.

Rajala T, Häkkinen A, Healy S, Yli-Harja O, Ribeiro AS - PLoS Comput. Biol. (2010)

Effects of a sequence-specific long-duration pause.Time interval between the completion of consecutive RNA molecules in a gene with 400 nucleotides in case (A) without long-duration pause sites, case (B) with one long-pause site at nucleotide 200 where kpause is half the value of the rate of stepwise elongation and dpause is 1 min, and case (C), identical to case (B) but with a 20% chance that a long-paused RNAP will lead to premature termination.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2837387&req=5

pcbi-1000704-g009: Effects of a sequence-specific long-duration pause.Time interval between the completion of consecutive RNA molecules in a gene with 400 nucleotides in case (A) without long-duration pause sites, case (B) with one long-pause site at nucleotide 200 where kpause is half the value of the rate of stepwise elongation and dpause is 1 min, and case (C), identical to case (B) but with a 20% chance that a long-paused RNAP will lead to premature termination.
Mentions: In Figure 9, the distribution of time intervals between transcription completion events in the three scenarios A, B, and C are shown. The effects of the probabilistic long-pauses and premature termination at nucleotide 200 are visible comparing the figures. We set a high transcription initiation rate so that, given the promoter open complex delay, transcription events are separated on average by 40±4 s intervals.

Bottom Line: We show that pauses' duration and rate of occurrence affect the bursting in RNA production, transcriptional and translational noise, and the transient to reach mean RNA and protein levels.In a genetic repressilator, increasing the pausing rate and the duration of pausing events increases the period length but does not affect the robustness of the periodicity.We conclude that RNA polymerase pausing might be an important evolvable feature of genetic networks.

View Article: PubMed Central - PubMed

Affiliation: Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, Tampere, Finland.

ABSTRACT
Stochasticity in gene expression affects many cellular processes and is a source of phenotypic diversity between genetically identical individuals. Events in elongation, particularly RNA polymerase pausing, are a source of this noise. Since the rate and duration of pausing are sequence-dependent, this regulatory mechanism of transcriptional dynamics is evolvable. The dependency of pause propensity on regulatory molecules makes pausing a response mechanism to external stress. Using a delayed stochastic model of bacterial transcription at the single nucleotide level that includes the promoter open complex formation, pausing, arrest, misincorporation and editing, pyrophosphorolysis, and premature termination, we investigate how RNA polymerase pausing affects a gene's transcriptional dynamics and gene networks. We show that pauses' duration and rate of occurrence affect the bursting in RNA production, transcriptional and translational noise, and the transient to reach mean RNA and protein levels. In a genetic repressilator, increasing the pausing rate and the duration of pausing events increases the period length but does not affect the robustness of the periodicity. We conclude that RNA polymerase pausing might be an important evolvable feature of genetic networks.

Show MeSH
Related in: MedlinePlus