BACKGROUND: We perform the theoretical analysis of a gene network sub-system, composed of a feed-forward loop, in which the upstream transcription factor regulates the target gene via two parallel pathways: directly, and via interaction with miRNA. RESULTS: As the molecular mechanisms of miRNA action are not clear so far, we elaborate three mathematical models, in which miRNA either represses translation of its target or promotes target mRNA degradation, or is not re-used, but degrades along with target mRNA. We examine the feed-forward loop dynamics quantitatively at the whole time interval of cell cycle. We rigorously proof the uniqueness of solutions to the models and obtain the exact solutions in one of them analytically. CONCLUSIONS: We have shown that different mechanisms of miRNA action lead to a variety of types of dynamical behavior of feed-forward loops. In particular, we found that the ability of feed-forward loop to dampen fluctuations introduced by transcription factor is the model and parameter dependent feature. We also discuss how our results could help a biologist to infer the mechanism of miRNA action.
BACKGROUND: We perform the theoretical analysis of a gene network sub-system, composed of a feed-forward loop, in which the upstream transcription factor regulates the target gene via two parallel pathways: directly, and via interaction with miRNA. RESULTS: As the molecular mechanisms of miRNA action are not clear so far, we elaborate three mathematical models, in which miRNA either represses translation of its target or promotes target mRNA degradation, or is not re-used, but degrades along with target mRNA. We examine the feed-forward loop dynamics quantitatively at the whole time interval of cell cycle. We rigorously proof the uniqueness of solutions to the models and obtain the exact solutions in one of them analytically. CONCLUSIONS: We have shown that different mechanisms of miRNA action lead to a variety of types of dynamical behavior of feed-forward loops. In particular, we found that the ability of feed-forward loop to dampen fluctuations introduced by transcription factor is the model and parameter dependent feature. We also discuss how our results could help a biologist to infer the mechanism of miRNA action.
Authors: Camile Castilho Fontelles; Luiza Nicolosi Guido; Mariana Papaléo Rosim; Fábia de Oliveira Andrade; Lu Jin; Jessica Inchauspe; Vanessa Cardoso Pires; Inar Alves de Castro; Leena Hilakivi-Clarke; Sonia de Assis; Thomas Prates Ong Journal: Breast Cancer Res Date: 2016-07-26 Impact factor: 6.466