1. Contributors: Charles Baker, Tao Jia and Rahul Kulkarni Department of Physics, Virginia Tech * Preprint available arXiv:1101.5861v2 Stochastic Model for Regulation of Gene Expression by Multiple Post-transcriptional Regulators (sRNAs) *

2. Outline Background – What is sRNA? Modeling Pathways with Multiple sRNAs – Extensions of Single sRNA Models * – Translational Bursting – Deriving Analytic Expressions Insights into Pathways – How do multiple sRNAs modulate Mean and Variance in Protein Distributions? Conclusions How do Multiple sRNAs Impact Stochastic Gene Expression? * T. Jia and R. V. Kulkarni, Physical Review Letters 105, 01801 (2010).

3. What is sRNA? Post-transcriptional regulators which bind to mRNA and impact mRNA degradation rate and/or translational efficiency Involved in major cellular pathways Multiple sRNAs often regulate single mRNA Often target key master regulators Global Regulation of Gene Expression Post-transcriptional Factor (i.e. sRNA)

4. Multiple sRNAs, One Target

5. Observations and Assumptions of sRNA Regulation * T. Jia and R. V. Kulkarni, Physical Review Letters 106, 058102 (2011).

6. Derivation of Analytic Expressions

7. Analytic Expressions How do Multiple sRNAs Alter Mean and Noise?

8. Method: Examine difference in Mean and Noise in regulated versus unregulated pathways Insight: In pathways with more than one regulator, mean and noise can be tuned simultaneously How Multiple sRNAs Tune Mean and Noise Mean Noise Mean Noise 1 sRNA Mean Noise Mean Noise >1 sRNA Fine tuning of protein distribution mean and noise could be achieved via evolution of new binding sites or rapidly in response to stimuli

9. New targets can arise from evolution of new binding sites The translational efficiency of new complexes impact the mean and noise in the regulated distribution Noise Dependence on Translational Rate

10. Fine Tuning in Response to Stress sRNAs can tune protein distribution noise in response to stimuli By altering sRNA concentration, the complex binding rate can be altered

11. Summary Method: Developed stochastic model for regulation by multiple sRNAs Results: Derived compact analytic expressions for mean and noise in protein distributions Insights: Expressions indicate multiple sRNAs can modulate mean and noise simultaneously Biological Relevance: Fine tuning in response to stimuli or through evolution of new binding sites

12. Questions?