Temperature-Dependent Model of Multi-step Transcription Initiation in Escherichia coli Based on Live Single-Cell Measurements.

Transcription kinetics is limited by its initiation steps, which differ between promoters and with intra- and extracellular conditions. Regulation of these steps allows tuning both the rate and stochasticity of RNA production. We used time-lapse, single-RNA microscopy measurements in live Escherichi...

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Main Authors: Samuel M D Oliveira, Antti Häkkinen, Jason Lloyd-Price, Huy Tran, Vinodh Kandavalli, Andre S Ribeiro
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-10-01
Series:PLoS Computational Biology
Online Access:http://europepmc.org/articles/PMC5085040?pdf=render
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author Samuel M D Oliveira
Antti Häkkinen
Jason Lloyd-Price
Huy Tran
Vinodh Kandavalli
Andre S Ribeiro
author_facet Samuel M D Oliveira
Antti Häkkinen
Jason Lloyd-Price
Huy Tran
Vinodh Kandavalli
Andre S Ribeiro
author_sort Samuel M D Oliveira
collection DOAJ
description Transcription kinetics is limited by its initiation steps, which differ between promoters and with intra- and extracellular conditions. Regulation of these steps allows tuning both the rate and stochasticity of RNA production. We used time-lapse, single-RNA microscopy measurements in live Escherichia coli to study how the rate-limiting steps in initiation of the Plac/ara-1 promoter change with temperature and induction scheme. For this, we compared detailed stochastic models fit to the empirical data in maximum likelihood sense using statistical methods. Using this analysis, we found that temperature affects the rate limiting steps unequally, as nonlinear changes in the closed complex formation suffice to explain the differences in transcription dynamics between conditions. Meanwhile, a similar analysis of the PtetA promoter revealed that it has a different rate limiting step configuration, with temperature regulating different steps. Finally, we used the derived models to explore a possible cause for why the identified steps are preferred as the main cause for behavior modifications with temperature: we find that transcription dynamics is either insensitive or responds reciprocally to changes in the other steps. Our results suggests that different promoters employ different rate limiting step patterns that control not only their rate and variability, but also their sensitivity to environmental changes.
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spelling doaj.art-bfd1f213d9034d0e878c9d146c5161a62022-12-22T03:38:20ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582016-10-011210e100517410.1371/journal.pcbi.1005174Temperature-Dependent Model of Multi-step Transcription Initiation in Escherichia coli Based on Live Single-Cell Measurements.Samuel M D OliveiraAntti HäkkinenJason Lloyd-PriceHuy TranVinodh KandavalliAndre S RibeiroTranscription kinetics is limited by its initiation steps, which differ between promoters and with intra- and extracellular conditions. Regulation of these steps allows tuning both the rate and stochasticity of RNA production. We used time-lapse, single-RNA microscopy measurements in live Escherichia coli to study how the rate-limiting steps in initiation of the Plac/ara-1 promoter change with temperature and induction scheme. For this, we compared detailed stochastic models fit to the empirical data in maximum likelihood sense using statistical methods. Using this analysis, we found that temperature affects the rate limiting steps unequally, as nonlinear changes in the closed complex formation suffice to explain the differences in transcription dynamics between conditions. Meanwhile, a similar analysis of the PtetA promoter revealed that it has a different rate limiting step configuration, with temperature regulating different steps. Finally, we used the derived models to explore a possible cause for why the identified steps are preferred as the main cause for behavior modifications with temperature: we find that transcription dynamics is either insensitive or responds reciprocally to changes in the other steps. Our results suggests that different promoters employ different rate limiting step patterns that control not only their rate and variability, but also their sensitivity to environmental changes.http://europepmc.org/articles/PMC5085040?pdf=render
spellingShingle Samuel M D Oliveira
Antti Häkkinen
Jason Lloyd-Price
Huy Tran
Vinodh Kandavalli
Andre S Ribeiro
Temperature-Dependent Model of Multi-step Transcription Initiation in Escherichia coli Based on Live Single-Cell Measurements.
PLoS Computational Biology
title Temperature-Dependent Model of Multi-step Transcription Initiation in Escherichia coli Based on Live Single-Cell Measurements.
title_full Temperature-Dependent Model of Multi-step Transcription Initiation in Escherichia coli Based on Live Single-Cell Measurements.
title_fullStr Temperature-Dependent Model of Multi-step Transcription Initiation in Escherichia coli Based on Live Single-Cell Measurements.
title_full_unstemmed Temperature-Dependent Model of Multi-step Transcription Initiation in Escherichia coli Based on Live Single-Cell Measurements.
title_short Temperature-Dependent Model of Multi-step Transcription Initiation in Escherichia coli Based on Live Single-Cell Measurements.
title_sort temperature dependent model of multi step transcription initiation in escherichia coli based on live single cell measurements
url http://europepmc.org/articles/PMC5085040?pdf=render
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