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Séminaire d'équipe(s) Bioinformatics
Mathematical modeling of miRNA-mediated mechanisms of translation regulation
Andrei Zinovyev

05 December 2013, 14:30
Salle/Bat : 475/PCRI-N
Contact :

Activités de recherche : System Biology

Résumé :
MicroRNAs can affect the protein translation using nine mechanistically different mechanisms, including repression of initiation and degradation of the transcript. There is a hot debate in the current literature about which mechanism and in which situations has a dominant role in living cells. The worst, same experimental systems dealing with the same pairs of mRNA and miRNA can provide ambiguous evidences about which is the actual mechanism of translation repression observed in the experiment. I review the current knowledge of various mechanisms of miRNA action and suggest that mathematical modeling can help resolving some of the controversial interpretations. I will introduce three simple mathematical models of mRNA translation in the presence of miRNA that can be used as tools in interpreting the experimental data on the dynamics of protein synthesis. The most complex model developed by us includes all known mechanisms of miRNA action. It allowed us to study possible dynamical patterns corresponding to different miRNA-mediated mechanisms of translation repression and to suggest concrete recipes on determining the dominant mechanism of miRNA action in the form of kinetic signatures. Using computational experiments and systematizing existing evidences from the literature, we justify a hypothesis about co-existence of distinct miRNA-mediated mechanisms of translation repression. The actually observed mechanism will be that acting on or changing the limiting “place” of the translation process. The limiting place can vary from one experimental setting to another. This hypothesis explains the majority of existing controversies reported.

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