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Gene regulation by a protein translation factor at the single-cell level

Authors: Roswitha Dolcemascolo; Lucas Goiriz; Roser Montagud-Martínez; Guillermo Rodrigo;
APC: 2,445.28 EUR

Gene regulation by a protein translation factor at the single-cell level

Abstract

Gene expression is inherently stochastic and pervasively regulated. While substantial work combining theory and experiments has been carried out to study how noise propagates through transcriptional regulations, the stochastic behavior of genes regulated at the level of translation is poorly understood. Here, we engineered a synthetic genetic system in which a target gene is down-regulated by a protein translation factor, which in turn is regulated transcriptionally. By monitoring both the expression of the regulator and the regulated gene at the single-cell level, we quantified the stochasticity of the system. We found that with a protein translation factor a tight repression can be achieved in single cells, noise propagation from gene to gene is buffered, and the regulated gene is sensitive in a nonlinear way to global perturbations in translation. A suitable mathematical model was instrumental to predict the transfer functions of the system. We also showed that a Gamma distribution parameterized with mesoscopic parameters, such as the mean expression and coefficient of variation, provides a deep analytical explanation about the system, displaying enough versatility to capture the cell-to-cell variability in genes regulated both transcriptionally and translationally. Overall, these results contribute to enlarge our understanding on stochastic gene expression, at the same time they provide design principles for synthetic biology.

Country
Spain
Keywords

Stochastic Processes, Gene Expression Regulation, Models, Genetic, Protein Biosynthesis, Synthetic Biology, Research Article

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
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8
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142
157
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