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. 2016:2016:2676282.
doi: 10.1155/2016/2676282. Epub 2016 Nov 10.

Effect of Dynamic Interaction between microRNA and Transcription Factor on Gene Expression

Affiliations

Effect of Dynamic Interaction between microRNA and Transcription Factor on Gene Expression

Qi Zhao et al. Biomed Res Int. 2016.

Abstract

MicroRNAs (miRNAs) are endogenous noncoding RNAs which participate in diverse biological processes in animals and plants. They are known to join together with transcription factors and downstream gene, forming a complex and highly interconnected regulatory network. To recognize a few overrepresented motifs which are expected to perform important elementary regulatory functions, we constructed a computational model of miRNA-mediated feedforward loops (FFLs) in which a transcription factor (TF) regulates miRNA and _targets gene. Based on the different dynamic interactions between miRNA and TF on gene expression, four possible structural topologies of FFLs with two gate functions (AND gate and OR gate) are introduced. We studied the dynamic behaviors of these different motifs. Furthermore, the relationship between the response time and maximal activation velocity of miRNA was investigated. We found that the curve of response time shows nonmonotonic behavior in Co1 loop with OR gate. This may help us to infer the mechanism of miRNA binding to the promoter region. At last we investigated the influence of important parameters on the dynamic response of system. We identified that the stationary levels of _target gene in all loops were insensitive to the initial value of miRNA.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
The coherent and incoherent feedforward loops. Arrows mean activation, the turned-over T-bars indicate repression. (a) Type 1 coherent FFL, TF activates _target gene and represses miRNA synthesis. (b) Type 2 coherent FFL, TF represses _target gene and activates miRNA synthesis. (c) Type 1 incoherent FFL, TF activates both _target gene and miRNA synthesis. (d) Type 2 incoherent FFL, TF represses both _target gene and miRNA synthesis.
Figure 2
Figure 2
The time evolutions of Z in various FFLs with different gate functions when k 1 is constant input. Types 1-2 coherent FFLs are shown in (a)-(b), while types 1-2 incoherent FFLs are given in (c)-(d). The red line corresponds to AND gate function, and the green line represents OR gate function. Here we fix k 1 = 0.25.
Figure 3
Figure 3
The time evolutions of Z in various FFLs with different gate functions in response to on and off steps of k 1. Types 1-2 coherent FFLs are shown in (a)-(b), while types 1-2 incoherent FFLs are given in (c)-(d). The red line corresponds to AND gate function, and the green line represents OR gate function. k 1 is set to 1 during the time between 50 and 100 and 0 in other time ranges (the black line).
Figure 4
Figure 4
The response time is plotted against the variation of v 2 in Co1 loop with different gate regulations. The red line corresponds to AND gate function, and the black line represents OR gate function. k 1 is set to 1 during the time between 50 and 100 and 0 in other time ranges.
Figure 5
Figure 5
The time evolutions of Z in various FFLs with different gate functions in response to variation of v 2. Types 1-2 coherent FFLs are shown in (a)-(b), while types 1-2 incoherent FFLs are given in (c)-(d). The red line corresponds to AND gate function, and the green line represents OR gate function. Here we fix k 1 = 0.25.
Figure 6
Figure 6
The time evolutions of Z in various FFLs with different gate functions in response to variation of d 2. Types 1-2 coherent FFLs are shown in (a)-(b), while types 1-2 incoherent FFLs are given in (c)-(d). The red line corresponds to AND gate function, and the green line represents OR gate function. Here we fix k 1 = 0.25.
Figure 7
Figure 7
The time evolutions of Z in various FFLs with different gate functions in response to variation of k 1. Types 1-2 coherent FFLs are shown in (a)-(b), while type 1-2 incoherent FFLs are given in (c)-(d). The red line corresponds to AND gate function, and the green line represents OR gate function. Here we fix k 1 = 0.25.
Figure 8
Figure 8
The time evolutions of Z in various FFLs with different gate functions in response to variation of d 1. Types 1-2 coherent FFLs are shown in (a)-(b), while types 1-2 incoherent FFLs are given in (c)-(d). The red line corresponds to AND gate function, and the green line represents OR gate function. Here we fix k 1 = 0.25.
Figure 9
Figure 9
The time evolutions of Z in various FFLs with different gate functions in response to the different initial values of miRNA. Types 1-2 coherent FFLs are shown in (a)-(b), while types 1-2 incoherent FFLs are given in (c)-(d). The red line corresponds to AND gate function, and the green line represents OR gate function. Here we choose three different initial values for Y, Y = 0, Y = 5, and Y = 20. We fix k 1 = 0.25.

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