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Multi-Target Regulation by Small RNAs Synchronizes Gene Expression Thresholds and May Enhance Ultrasensitive Behavior

Abstract:

Cells respond to external cues by precisely coordinating multiple molecular events. Co-regulation may be established by the so-called single-input module (SIM), where a common regulator controls multiple targets. Using mathematical modeling, we compared the ability of SIM architectures to precisely coordinate protein levels despite environmental fluctuations and uncertainties in parameter values. We find that post-transcriptional co-regulation as exemplified by bacterial small RNAs (sRNAs) is particularly robust: sRNA-mediated regulation establishes highly synchronous gene expression thresholds for all mRNA targets without a need for fine-tuning of kinetic parameters. Our analyses reveal that the non-catalytic nature of sRNA action is essential for robust gene expression synchronization, and that sRNA sequestration effects underlie coupling of multiple mRNA pools. This principle also operates in the temporal regime, implying that sRNAs could robustly coordinate the kinetics of mRNA induction as well. Moreover, we observe that multi-target regulation by a small RNA can strongly enhance ultrasensitivity in mRNA expression when compared to the single-target case. Our findings may explain why bacterial small RNAs frequently coordinate all-or-none responses to cellular stress.

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Projects: A2.4: Linking signalling pathways regulating liver regeneration and orga..., B1.3: Linking modulation of iron metabolism with the impact of macrophag...

PLoS ONE
PLoS ONE 7(8): e42296
21st Aug 2012

Jörn Matthias Schmiedel, Ilka Maria Axmann, Stefan Legewie

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[Stefan Legewie]

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Cell
Views: 1843
  • Created: 3rd Sep 2012 at 11:02
  • Last updated: 24th Oct 2013 at 16:16

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