Limits...
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 response time is plotted against the variation of v2 in Co1 loop with different gate regulations. The red line corresponds to AND gate function, and the black line represents OR gate function. k1 is set to 1 during the time between 50 and 100 and 0 in other time ranges.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5121577&req=5

fig4: The response time is plotted against the variation of v2 in Co1 loop with different gate regulations. The red line corresponds to AND gate function, and the black line represents OR gate function. k1 is set to 1 during the time between 50 and 100 and 0 in other time ranges.

Mentions: The response time is a measure of the time which a gene product takes to reach its physiologically determined steady state level. The speed of the response is characterized by the response time, which Z takes to reach half of its steady state level. Here v2 is the maximal activation velocity of miRNA by TF. In Figure 4, we study the relationship between the response time and v2 in Co1 loop with both gate regulations when providing the system with simultaneous pulse. We can observe that the response time has a form of increasing function as v2 turns bigger in Co1 loop with AND gate, which means the system responses more slowly as v2 increases. This is easy to understand; larger v2 induces more miRNA generation which further represses target gene synthesis, so the response time turns slowly. But for the case in Co1 loop with OR gate, the response time shows nonmonotonic behavior, which first climbs and then damps as further increasing v2. This indicates that there exists a value of v2 such that the system responses most slowly. To understand this, we need to refer to OR gate function we use. It is a nonmonotonic function as v2 increases, so the form of function decides the speed of the response of the system. Our result here might be useful to infer the mechanism of miRNA binding to the promoter region, whether or not the TF and miRNA compete for binding to the target gene. Also, we obtain that the response of gene expression in Co1 loop with OR gate is faster than that in Co1 loop with AND gate during the period of v2 changing.


Effect of Dynamic Interaction between microRNA and Transcription Factor on Gene Expression
The response time is plotted against the variation of v2 in Co1 loop with different gate regulations. The red line corresponds to AND gate function, and the black line represents OR gate function. k1 is set to 1 during the time between 50 and 100 and 0 in other time ranges.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121577&req=5

fig4: The response time is plotted against the variation of v2 in Co1 loop with different gate regulations. The red line corresponds to AND gate function, and the black line represents OR gate function. k1 is set to 1 during the time between 50 and 100 and 0 in other time ranges.
Mentions: The response time is a measure of the time which a gene product takes to reach its physiologically determined steady state level. The speed of the response is characterized by the response time, which Z takes to reach half of its steady state level. Here v2 is the maximal activation velocity of miRNA by TF. In Figure 4, we study the relationship between the response time and v2 in Co1 loop with both gate regulations when providing the system with simultaneous pulse. We can observe that the response time has a form of increasing function as v2 turns bigger in Co1 loop with AND gate, which means the system responses more slowly as v2 increases. This is easy to understand; larger v2 induces more miRNA generation which further represses target gene synthesis, so the response time turns slowly. But for the case in Co1 loop with OR gate, the response time shows nonmonotonic behavior, which first climbs and then damps as further increasing v2. This indicates that there exists a value of v2 such that the system responses most slowly. To understand this, we need to refer to OR gate function we use. It is a nonmonotonic function as v2 increases, so the form of function decides the speed of the response of the system. Our result here might be useful to infer the mechanism of miRNA binding to the promoter region, whether or not the TF and miRNA compete for binding to the target gene. Also, we obtain that the response of gene expression in Co1 loop with OR gate is faster than that in Co1 loop with AND gate during the period of v2 changing.

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.