%0 Journal Article %1 Rajala2010Effects %A Rajala, Tiina %A Häkkinen, Antti %A Healy, Shannon %A Yli-Harja, Olli %A Ribeiro, Andre S. %D 2010 %I Public Library of Science %J PLoS computational biology %K dynamics gene-expression stochasticity %N 3 %P e1000704+ %R 10.1371/journal.pcbi.1000704 %T Effects of transcriptional pausing on gene expression dynamics. %U http://dx.doi.org/10.1371/journal.pcbi.1000704 %V 6 %X 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.

@article{Rajala2010Effects, 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.}, added-at = {2018-12-02T16:09:07.000+0100}, author = {Rajala, Tiina and H\"{a}kkinen, Antti and Healy, Shannon and Yli-Harja, Olli and Ribeiro, Andre S.}, biburl = {https://www.bibsonomy.org/bibtex/27c8d3793706dcaab6ef5591ef276745b/karthikraman}, citeulike-article-id = {6819938}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pcbi.1000704}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/20300642}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=20300642}, day = 12, doi = {10.1371/journal.pcbi.1000704}, interhash = {362a70098f430e9bd3bbd8c670e6d7dd}, intrahash = {7c8d3793706dcaab6ef5591ef276745b}, issn = {1553-7358}, journal = {PLoS computational biology}, keywords = {dynamics gene-expression stochasticity}, month = mar, number = 3, pages = {e1000704+}, pmid = {20300642}, posted-at = {2010-03-12 08:59:59}, priority = {2}, publisher = {Public Library of Science}, timestamp = {2018-12-02T16:09:07.000+0100}, title = {Effects of transcriptional pausing on gene expression dynamics.}, url = {http://dx.doi.org/10.1371/journal.pcbi.1000704}, volume = 6, year = 2010 }