Beyond initiation-limited translational bursting: the effects of burst size distributions on the stability of gene expression

Handle URI:
http://hdl.handle.net/10754/583861
Title:
Beyond initiation-limited translational bursting: the effects of burst size distributions on the stability of gene expression
Authors:
Kuwahara, Hiroyuki; Arold, Stefan T. ( 0000-0001-5278-0668 ) ; Gao, Xin ( 0000-0002-7108-3574 )
Abstract:
A main source of gene expression noise in prokaryotes is translational bursting. It arises from efficient translation of mRNAs with low copy numbers, which makes the production of protein copies highly variable and pulsatile. To obtain analytical solutions, previous models to capture this noise source had to assume translation to be initiation-limited, representing the burst size by a specific type of a long-tail distribution. However, there is increasing evidence suggesting that the initiation is not the rate-limiting step in certain settings, for example, under stress conditions. Here, to overcome the limitations imposed by the initiation-limited assumption, we present a new analytical approach that can evaluate biological consequences of the protein burst size with a general distribution. Since our new model can capture the contribution of other factors to the translational noise, it can be used to analyze the effects of gene expression noise in more general settings. We used this new model to analytically analyze the connection between the burst size and the stability of gene expression processes in various settings. We found that the burst size with different distributions can lead to quantitatively and qualitatively different stability characteristics of protein abundance and can have non-intuitive effects. By allowing analysis of how the stability of gene expression processes changes based on various distributions of translational noise, our analytical approach is expected to enable deeper insights into the control of cell fate decision-making, the evolution of cryptic genetic variations, and fine-tuning of gene circuits.
KAUST Department:
Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division; Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Beyond initiation-limited translational bursting: the effects of burst size distributions on the stability of gene expression 2015, 7 (12):1622 Integr. Biol.
Publisher:
Royal Society of Chemistry (RSC)
Journal:
Integr. Biol.
Issue Date:
4-Nov-2015
DOI:
10.1039/C5IB00107B
PubMed ID:
26566069
Type:
Article
ISSN:
1757-9694; 1757-9708
Additional Links:
http://xlink.rsc.org/?DOI=C5IB00107B
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorKuwahara, Hiroyukien
dc.contributor.authorArold, Stefan T.en
dc.contributor.authorGao, Xinen
dc.date.accessioned2015-12-14T08:07:27Zen
dc.date.available2015-12-14T08:07:27Zen
dc.date.issued2015-11-04en
dc.identifier.citationBeyond initiation-limited translational bursting: the effects of burst size distributions on the stability of gene expression 2015, 7 (12):1622 Integr. Biol.en
dc.identifier.issn1757-9694en
dc.identifier.issn1757-9708en
dc.identifier.pmid26566069-
dc.identifier.doi10.1039/C5IB00107Ben
dc.identifier.urihttp://hdl.handle.net/10754/583861en
dc.description.abstractA main source of gene expression noise in prokaryotes is translational bursting. It arises from efficient translation of mRNAs with low copy numbers, which makes the production of protein copies highly variable and pulsatile. To obtain analytical solutions, previous models to capture this noise source had to assume translation to be initiation-limited, representing the burst size by a specific type of a long-tail distribution. However, there is increasing evidence suggesting that the initiation is not the rate-limiting step in certain settings, for example, under stress conditions. Here, to overcome the limitations imposed by the initiation-limited assumption, we present a new analytical approach that can evaluate biological consequences of the protein burst size with a general distribution. Since our new model can capture the contribution of other factors to the translational noise, it can be used to analyze the effects of gene expression noise in more general settings. We used this new model to analytically analyze the connection between the burst size and the stability of gene expression processes in various settings. We found that the burst size with different distributions can lead to quantitatively and qualitatively different stability characteristics of protein abundance and can have non-intuitive effects. By allowing analysis of how the stability of gene expression processes changes based on various distributions of translational noise, our analytical approach is expected to enable deeper insights into the control of cell fate decision-making, the evolution of cryptic genetic variations, and fine-tuning of gene circuits.en
dc.language.isoenen
dc.publisherRoyal Society of Chemistry (RSC)en
dc.relation.urlhttp://xlink.rsc.org/?DOI=C5IB00107Ben
dc.rightsArchived with thanks to Integr. Biol.en
dc.titleBeyond initiation-limited translational bursting: the effects of burst size distributions on the stability of gene expressionen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalIntegr. Biol.en
dc.eprint.versionPost-printen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorKuwahara, Hiroyukien
kaust.authorArold, Stefan T.en
kaust.authorGao, Xinen

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