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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


The time evolutions of Z in various FFLs with different gate functions in response to variation of d1. 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 k1 = 0.25.
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fig8: The time evolutions of Z in various FFLs with different gate functions in response to variation of d1. 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 k1 = 0.25.

Mentions: We also investigate the effect of changes in k1 and d1 on the dynamical behavior of Z (Figures 7 and 8). In Co1 loop, bigger k1 induces more Z with both gate functions, while, in Co2 loop, the situation is opposite; lager k1 makes less Z with both gate functions. This is due to the fact that TF activates target gene directly and promotes it indirectly in Co1 loop, while, in Co2 loop, TF inhibits target gene directly and represses it indirectly. For the cases in In1 and In2 loops with OR gate, both lager k1 and small k1 generate nearly the same stationary level of Z which is higher than what the original value makes. For the cases in In1 and In2 loops with AND gate, both lager k1 and small k1 induce nearly the same stationary level of Z which is slightly lower than that induced by the original value. For the variations of d1 (Figure 8), we get similar results in In1 and In2 loops with both gates, but with the opposite results in Co1 and Co2 loops. Furthermore, we study the effect of different initial values of miRNA on the response of the system (Figure 9). We find that the different initial values of miRNA have no significant influence on the steady state of target gene after it passes the transient state.


Effect of Dynamic Interaction between microRNA and Transcription Factor on Gene Expression
The time evolutions of Z in various FFLs with different gate functions in response to variation of d1. 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 k1 = 0.25.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5121577&req=5

fig8: The time evolutions of Z in various FFLs with different gate functions in response to variation of d1. 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 k1 = 0.25.
Mentions: We also investigate the effect of changes in k1 and d1 on the dynamical behavior of Z (Figures 7 and 8). In Co1 loop, bigger k1 induces more Z with both gate functions, while, in Co2 loop, the situation is opposite; lager k1 makes less Z with both gate functions. This is due to the fact that TF activates target gene directly and promotes it indirectly in Co1 loop, while, in Co2 loop, TF inhibits target gene directly and represses it indirectly. For the cases in In1 and In2 loops with OR gate, both lager k1 and small k1 generate nearly the same stationary level of Z which is higher than what the original value makes. For the cases in In1 and In2 loops with AND gate, both lager k1 and small k1 induce nearly the same stationary level of Z which is slightly lower than that induced by the original value. For the variations of d1 (Figure 8), we get similar results in In1 and In2 loops with both gates, but with the opposite results in Co1 and Co2 loops. Furthermore, we study the effect of different initial values of miRNA on the response of the system (Figure 9). We find that the different initial values of miRNA have no significant influence on the steady state of target gene after it passes the transient state.

View Article: PubMed Central - PubMed

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.

No MeSH data available.