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Dynamics of miRNA driven feed-forward loop depends upon miRNA action mechanisms

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 actio...

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Detalles Bibliográficos
Autores principales: Duk, Maria A, Samsonova, Maria G, Samsonov, Alexander M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303955/
https://www.ncbi.nlm.nih.gov/pubmed/25563303
http://dx.doi.org/10.1186/1471-2164-15-S12-S9
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author Duk, Maria A
Samsonova, Maria G
Samsonov, Alexander M
author_facet Duk, Maria A
Samsonova, Maria G
Samsonov, Alexander M
author_sort Duk, Maria A
collection PubMed
description 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.
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spelling pubmed-43039552015-02-09 Dynamics of miRNA driven feed-forward loop depends upon miRNA action mechanisms Duk, Maria A Samsonova, Maria G Samsonov, Alexander M BMC Genomics Research 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. BioMed Central 2014-12-19 /pmc/articles/PMC4303955/ /pubmed/25563303 http://dx.doi.org/10.1186/1471-2164-15-S12-S9 Text en Copyright © 2014 Duk et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Duk, Maria A
Samsonova, Maria G
Samsonov, Alexander M
Dynamics of miRNA driven feed-forward loop depends upon miRNA action mechanisms
title Dynamics of miRNA driven feed-forward loop depends upon miRNA action mechanisms
title_full Dynamics of miRNA driven feed-forward loop depends upon miRNA action mechanisms
title_fullStr Dynamics of miRNA driven feed-forward loop depends upon miRNA action mechanisms
title_full_unstemmed Dynamics of miRNA driven feed-forward loop depends upon miRNA action mechanisms
title_short Dynamics of miRNA driven feed-forward loop depends upon miRNA action mechanisms
title_sort dynamics of mirna driven feed-forward loop depends upon mirna action mechanisms
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303955/
https://www.ncbi.nlm.nih.gov/pubmed/25563303
http://dx.doi.org/10.1186/1471-2164-15-S12-S9
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