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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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Threshold-Linear Response of a Target Gene(A) and (B) depict an idealized model for the interaction between mRNAs of a target gene and sRNAs. If the sRNA transcription rate is larger than that of the target (A), then gene expression is silenced, whereas if sRNA is transcribed less efficiently than its target (B), the residual unbound mRNAs code for proteins.(C) Predicted response curve of a target gene. The blue line depicts the idealized threshold-linear mode of regulation in which gene expression is completely silenced if the target transcription rate is below a threshold set by the transcription rate of the sRNA (indicated by the dashed line). Above this threshold, gene expression increases linearly with the difference between the mRNA and sRNA transcription rates. The idealized scenario is expected when binding between sRNA and mRNA occurs extremely rapidly. The red line is the actual response expected according to Equation 2, using the estimated parameters of Table 1, column 3 for αs = 1 nM/min.
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pbio-0050229-g001: Threshold-Linear Response of a Target Gene(A) and (B) depict an idealized model for the interaction between mRNAs of a target gene and sRNAs. If the sRNA transcription rate is larger than that of the target (A), then gene expression is silenced, whereas if sRNA is transcribed less efficiently than its target (B), the residual unbound mRNAs code for proteins.(C) Predicted response curve of a target gene. The blue line depicts the idealized threshold-linear mode of regulation in which gene expression is completely silenced if the target transcription rate is below a threshold set by the transcription rate of the sRNA (indicated by the dashed line). Above this threshold, gene expression increases linearly with the difference between the mRNA and sRNA transcription rates. The idealized scenario is expected when binding between sRNA and mRNA occurs extremely rapidly. The red line is the actual response expected according to Equation 2, using the estimated parameters of Table 1, column 3 for αs = 1 nM/min.

Mentions: The noncatalytic nature of sRNA-mediated gene regulation suggests a novel threshold-linear mode of action, by which the expression of a target gene is silenced below a threshold, and is gradually activated above it (Figure 1). Consider first a case where sRNA and mRNA are co-degraded in a one-to-one fashion. In this case, if the transcription rate for the target mRNA (αm) is below that for the sRNA (αs) (Figure 1A), then most of the targets are expected to pair with the sRNAs and be rapidly degraded, as suggested recently by Lenz et al. [7]. Conversely, if the transcription rate of the mRNA exceeds that of the sRNA (Figure 1B), then most of the sRNAs are expected to turnover, whereas the unconsumed mRNAs are free to be translated into proteins. In the latter regime, the expressed protein level would reflect the difference between the two transcription rates. This scenario is summarized by the blue line in Figure 1C, where the steady state mRNA level of the target gene (m) is plotted against its transcription rate (αm). Messenger RNAs are expected to accumulate only if the target transcription rate exceeds the threshold, which is given by the transcription rate of the sRNA αs (vertical dashed line).


Quantitative characteristics of gene regulation by small RNA.

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

Threshold-Linear Response of a Target Gene(A) and (B) depict an idealized model for the interaction between mRNAs of a target gene and sRNAs. If the sRNA transcription rate is larger than that of the target (A), then gene expression is silenced, whereas if sRNA is transcribed less efficiently than its target (B), the residual unbound mRNAs code for proteins.(C) Predicted response curve of a target gene. The blue line depicts the idealized threshold-linear mode of regulation in which gene expression is completely silenced if the target transcription rate is below a threshold set by the transcription rate of the sRNA (indicated by the dashed line). Above this threshold, gene expression increases linearly with the difference between the mRNA and sRNA transcription rates. The idealized scenario is expected when binding between sRNA and mRNA occurs extremely rapidly. The red line is the actual response expected according to Equation 2, using the estimated parameters of Table 1, column 3 for αs = 1 nM/min.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-0050229-g001: Threshold-Linear Response of a Target Gene(A) and (B) depict an idealized model for the interaction between mRNAs of a target gene and sRNAs. If the sRNA transcription rate is larger than that of the target (A), then gene expression is silenced, whereas if sRNA is transcribed less efficiently than its target (B), the residual unbound mRNAs code for proteins.(C) Predicted response curve of a target gene. The blue line depicts the idealized threshold-linear mode of regulation in which gene expression is completely silenced if the target transcription rate is below a threshold set by the transcription rate of the sRNA (indicated by the dashed line). Above this threshold, gene expression increases linearly with the difference between the mRNA and sRNA transcription rates. The idealized scenario is expected when binding between sRNA and mRNA occurs extremely rapidly. The red line is the actual response expected according to Equation 2, using the estimated parameters of Table 1, column 3 for αs = 1 nM/min.
Mentions: The noncatalytic nature of sRNA-mediated gene regulation suggests a novel threshold-linear mode of action, by which the expression of a target gene is silenced below a threshold, and is gradually activated above it (Figure 1). Consider first a case where sRNA and mRNA are co-degraded in a one-to-one fashion. In this case, if the transcription rate for the target mRNA (αm) is below that for the sRNA (αs) (Figure 1A), then most of the targets are expected to pair with the sRNAs and be rapidly degraded, as suggested recently by Lenz et al. [7]. Conversely, if the transcription rate of the mRNA exceeds that of the sRNA (Figure 1B), then most of the sRNAs are expected to turnover, whereas the unconsumed mRNAs are free to be translated into proteins. In the latter regime, the expressed protein level would reflect the difference between the two transcription rates. This scenario is summarized by the blue line in Figure 1C, where the steady state mRNA level of the target gene (m) is plotted against its transcription rate (αm). Messenger RNAs are expected to accumulate only if the target transcription rate exceeds the threshold, which is given by the transcription rate of the sRNA αs (vertical dashed line).

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