Biology – Quantitative Biology – Molecular Networks
Scientific paper
2012-02-06
Biology
Quantitative Biology
Molecular Networks
38 pages, 8 figures, 4 tables, 90 cited references. arXiv admin note: substantial text overlap with arXiv:0911.1797
Scientific paper
MicroRNA 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 controversial evidences about which is the actual mechanism of translation repression observed in the experiment. We start with reviewing the current state of the art about the knowledge of various mechanisms of miRNA action and suggest that mathematical modeling can help resolving some of the controversial interpretations. We describe three simple mathematical models of miRNA translation 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 the limiting step of translation which might vary from one experimental setting to another. This model explains the majority of existing controversies reported.
Gorban Alexander N.
Harel-Belan A.
Morozova Nadya
Zinovyev Andrei
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