Systems Biology Mini Symposium - SDI - Matteo OSELLA - MicroRNA-mediated feed forward loops function as noise buffers : a stochastic model and simulations Dec. 9, 2009

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Matteo OSELLA II) MicroRNA-mediated feed forward loops function as noise buffers : a stochastic model and simulations. MicroRNAs are endogenous non coding RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNA of protein-coding genes to direct their post-transcriptional repression. In particular the microRNA-mediated feed forward loops (coherent and incoherent) seem to be a motif (an overrepresented regulatory circuit) in the mixed network of transcriptional and microRNA regulations. We show analytically and through simulations that the incoherent version of this circuit can function as a noise buffer, reducing fluctuations in protein production. Moreover our model predicts that the optimal attenuation of fluctuations coincides with a modest strength of repression, in agreement with experimental observations of the actual impact of a wide class of miRNAs on the protein output of their targets. Finally the intrinsic non-linearity of the process can give birth to non trivial deviant effects (deviation from the mean field description) that cannot be fully described by linearized models.

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