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Mardi 21 fevrier 2012-14:00

Theory of post-transcriptional regulation in biological systems

Daniel Jost (Harvard University, USA)

par Bertrand Georgeot - 21 février 2012

Small RNA (sRNA) play critical regulatory roles in organisms across all kingdoms of life : from the control of stress response in bacteria to the regulation of development in animals. sRNAs act at the post-transcriptional level via base-pairing with the targeted messenger RNAs (mRNA), leading to suppression of translation and/or to promotion of degradation of the mRNA. In this talk, I will present my work on the modeling of the sRNA regulation. In a first part, I will discuss the Langevin-like model we use to describe the stochastic dynamic of the coupled system composed by the sRNA and its targets. In particular, our formalism accounts for the stochastic nature of the underlying biochemical reactions, including the effect of transport by diffusion of the interacting molecules. I will also present the general physical properties of this type of regulation. In particular, we will discuss the fluctuations of the system that we estimated using the fluctuation-dissipation theorem derived from the linear-noise approximation. In a second part, I will apply this formalism to concrete biological situations. In particular : 1) Our model suggest that the presence of weak targets (which make transient complexes with the sRNAs) helps maintaining the intrinsic fluctuations of the main/strong targets at a low level, without significantly affecting their mean responses. 2) In the context of bacterial regulation, a detailed modeling of the translation process coupled to our stochastic description of sRNA regulation, suggest that ribosomes recruit sRNA molecules and that an increase of the affinity between the ribosome and the mRNA leads to a more efficient but more noisy regulation of the target.