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Quantitative characteristics of gene regulation by small RNA.

Levine E, Zhang Z, Kuhlman T, Hwa T - PLoS Biol. (2007)

Bottom Line: Our results demonstrate that sRNA provides a novel mode of gene regulation, with characteristics distinct from those of protein-mediated gene regulation.Knowledge of these special features of sRNA-mediated regulation may be crucial toward understanding the subtle functions that sRNAs can play in coordinating various stress-relief pathways.Our results may also help guide the design of synthetic genetic circuits that have properties difficult to attain with protein regulators alone.

View Article: PubMed Central - PubMed

Affiliation: Center for Theoretical Biological Physics, University of California San Diego, La Jolla, California, United States of America.

ABSTRACT
An increasing number of small RNAs (sRNAs) have been shown to regulate critical pathways in prokaryotes and eukaryotes. In bacteria, regulation by trans-encoded sRNAs is predominantly found in the coordination of intricate stress responses. The mechanisms by which sRNAs modulate expression of its targets are diverse. In common to most is the possibility that interference with the translation of mRNA targets may also alter the abundance of functional sRNAs. Aiming to understand the unique role played by sRNAs in gene regulation, we studied examples from two distinct classes of bacterial sRNAs in Escherichia coli using a quantitative approach combining experiment and theory. Our results demonstrate that sRNA provides a novel mode of gene regulation, with characteristics distinct from those of protein-mediated gene regulation. These include a threshold-linear response with a tunable threshold, a robust noise resistance characteristic, and a built-in capability for hierarchical cross-talk. Knowledge of these special features of sRNA-mediated regulation may be crucial toward understanding the subtle functions that sRNAs can play in coordinating various stress-relief pathways. Our results may also help guide the design of synthetic genetic circuits that have properties difficult to attain with protein regulators alone.

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Related in: MedlinePlus

Comparison between sRNA- and Protein-Mediated Repression(A) Steady-state solution of model (1), with the estimated parameters of Table 1. The strength of sRNA repression decreases as the target transcription increases. (B) Steady-state solution of a model for protein regulators (Supporting Text S1), where the strength of repression is independent of target transcription rate. (C) Temporal behavior in a single stochastic simulation [94] of the expression of two model genes, geneA (blue line) and geneP (red), regulated by sRNA and protein regulators respectively. For geneA we set αA = 1/min and kA = 0.02/min, while for geneP we have αP = 0.0043/min and kP = 0. All other parameters are taken from Table 1 and are identical for both genes. This choice of parameters makes the mean mRNA levels of the two genes equal. The bursty nature of the noise for geneP is compared with the smooth fluctuations exhibited by geneA.
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pbio-0050229-g005: Comparison between sRNA- and Protein-Mediated Repression(A) Steady-state solution of model (1), with the estimated parameters of Table 1. The strength of sRNA repression decreases as the target transcription increases. (B) Steady-state solution of a model for protein regulators (Supporting Text S1), where the strength of repression is independent of target transcription rate. (C) Temporal behavior in a single stochastic simulation [94] of the expression of two model genes, geneA (blue line) and geneP (red), regulated by sRNA and protein regulators respectively. For geneA we set αA = 1/min and kA = 0.02/min, while for geneP we have αP = 0.0043/min and kP = 0. All other parameters are taken from Table 1 and are identical for both genes. This choice of parameters makes the mean mRNA levels of the two genes equal. The bursty nature of the noise for geneP is compared with the smooth fluctuations exhibited by geneA.

Mentions: Analysis of a simple model of protein-mediated gene regulation (Text S1) predicts that regardless of whether a protein regulator acts as a transcriptional repressor or as a catalyst of mRNA degradation, target expression always increases linearly with the promoter activity. The ratio between expression levels at different concentrations of the regulator is independent of the target activity (Figure 5B). Thus, one can safely talk about the strength of repression in term of the fold-change in gene expression in the presence and absence of the repressor without referring to the rate of target transcription.


Quantitative characteristics of gene regulation by small RNA.

Levine E, Zhang Z, Kuhlman T, Hwa T - PLoS Biol. (2007)

Comparison between sRNA- and Protein-Mediated Repression(A) Steady-state solution of model (1), with the estimated parameters of Table 1. The strength of sRNA repression decreases as the target transcription increases. (B) Steady-state solution of a model for protein regulators (Supporting Text S1), where the strength of repression is independent of target transcription rate. (C) Temporal behavior in a single stochastic simulation [94] of the expression of two model genes, geneA (blue line) and geneP (red), regulated by sRNA and protein regulators respectively. For geneA we set αA = 1/min and kA = 0.02/min, while for geneP we have αP = 0.0043/min and kP = 0. All other parameters are taken from Table 1 and are identical for both genes. This choice of parameters makes the mean mRNA levels of the two genes equal. The bursty nature of the noise for geneP is compared with the smooth fluctuations exhibited by geneA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1994261&req=5

pbio-0050229-g005: Comparison between sRNA- and Protein-Mediated Repression(A) Steady-state solution of model (1), with the estimated parameters of Table 1. The strength of sRNA repression decreases as the target transcription increases. (B) Steady-state solution of a model for protein regulators (Supporting Text S1), where the strength of repression is independent of target transcription rate. (C) Temporal behavior in a single stochastic simulation [94] of the expression of two model genes, geneA (blue line) and geneP (red), regulated by sRNA and protein regulators respectively. For geneA we set αA = 1/min and kA = 0.02/min, while for geneP we have αP = 0.0043/min and kP = 0. All other parameters are taken from Table 1 and are identical for both genes. This choice of parameters makes the mean mRNA levels of the two genes equal. The bursty nature of the noise for geneP is compared with the smooth fluctuations exhibited by geneA.
Mentions: Analysis of a simple model of protein-mediated gene regulation (Text S1) predicts that regardless of whether a protein regulator acts as a transcriptional repressor or as a catalyst of mRNA degradation, target expression always increases linearly with the promoter activity. The ratio between expression levels at different concentrations of the regulator is independent of the target activity (Figure 5B). Thus, one can safely talk about the strength of repression in term of the fold-change in gene expression in the presence and absence of the repressor without referring to the rate of target transcription.

Bottom Line: Our results demonstrate that sRNA provides a novel mode of gene regulation, with characteristics distinct from those of protein-mediated gene regulation.Knowledge of these special features of sRNA-mediated regulation may be crucial toward understanding the subtle functions that sRNAs can play in coordinating various stress-relief pathways.Our results may also help guide the design of synthetic genetic circuits that have properties difficult to attain with protein regulators alone.

View Article: PubMed Central - PubMed

Affiliation: Center for Theoretical Biological Physics, University of California San Diego, La Jolla, California, United States of America.

ABSTRACT
An increasing number of small RNAs (sRNAs) have been shown to regulate critical pathways in prokaryotes and eukaryotes. In bacteria, regulation by trans-encoded sRNAs is predominantly found in the coordination of intricate stress responses. The mechanisms by which sRNAs modulate expression of its targets are diverse. In common to most is the possibility that interference with the translation of mRNA targets may also alter the abundance of functional sRNAs. Aiming to understand the unique role played by sRNAs in gene regulation, we studied examples from two distinct classes of bacterial sRNAs in Escherichia coli using a quantitative approach combining experiment and theory. Our results demonstrate that sRNA provides a novel mode of gene regulation, with characteristics distinct from those of protein-mediated gene regulation. These include a threshold-linear response with a tunable threshold, a robust noise resistance characteristic, and a built-in capability for hierarchical cross-talk. Knowledge of these special features of sRNA-mediated regulation may be crucial toward understanding the subtle functions that sRNAs can play in coordinating various stress-relief pathways. Our results may also help guide the design of synthetic genetic circuits that have properties difficult to attain with protein regulators alone.

Show MeSH
Related in: MedlinePlus