Conversion of a stable fixed point into a transient peak by stochastic fluctuation in a gene regulatory network

Author(s):  
Julian Lee
2018 ◽  
Author(s):  
JaeJun Lee ◽  
Julian Lee

AbstractIn a stochastic process, noise often modifies the picture offered by the mean field dynamics. In particular, when there is an absorbing state, the noise erases a stable fixed point of the mean field equation from the stationary distribution, and turns it into a transient peak. We make a quantitative analysis of this effect for a simple genetic regulatory network with positive feedback, where the proteins become extinct in the presence of stochastic noise, contrary to the prediction of the deterministic rate equation that the protein number converges to a non-zero value. We show that the transient peak appears near the stable fixed point of the rate equation, and the extinction time diverges exponentially as the stochastic noise approaches zero. We also show how the baseline production from the inactive gene ameliorates the effect of the stochastic noise, and interpret the opposite effects of the noise and the baseline production in terms of the position shift of the unstable fixed point. The order of magnitude estimates using biological parameters suggest that for a real gene regulatory network, the stochastic noise is sufficiently small so that not only is the extinction time much larger than biologically relevant time-scales, but also the effect of the baseline production dominates over that of the stochastic noise, leading to the protection from the catastrophic rare event of protein extinction.


Author(s):  
Xingzhe Yang ◽  
Feng Li ◽  
Jie Ma ◽  
Yan Liu ◽  
Xuejiao Wang ◽  
...  

AbstractIn recent years, the incidence of fatigue has been increasing, and the effective prevention and treatment of fatigue has become an urgent problem. As a result, the genetic research of fatigue has become a hot spot. Transcriptome-level regulation is the key link in the gene regulatory network. The transcriptome includes messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). MRNAs are common research targets in gene expression profiling. Noncoding RNAs, including miRNAs, lncRNAs, circRNAs and so on, have been developed rapidly. Studies have shown that miRNAs are closely related to the occurrence and development of fatigue. MiRNAs can regulate the immune inflammatory reaction in the central nervous system (CNS), regulate the transmission of nerve impulses and gene expression, regulate brain development and brain function, and participate in the occurrence and development of fatigue by regulating mitochondrial function and energy metabolism. LncRNAs can regulate dopaminergic neurons to participate in the occurrence and development of fatigue. This has certain value in the diagnosis of chronic fatigue syndrome (CFS). CircRNAs can participate in the occurrence and development of fatigue by regulating the NF-κB pathway, TNF-α and IL-1β. The ceRNA hypothesis posits that in addition to the function of miRNAs in unidirectional regulation, mRNAs, lncRNAs and circRNAs can regulate gene expression by competitive binding with miRNAs, forming a ceRNA regulatory network with miRNAs. Therefore, we suggest that the miRNA-centered ceRNA regulatory network is closely related to fatigue. At present, there are few studies on fatigue-related ncRNA genes, and most of these limited studies are on miRNAs in ncRNAs. However, there are a few studies on the relationship between lncRNAs, cirRNAs and fatigue. Less research is available on the pathogenesis of fatigue based on the ceRNA regulatory network. Therefore, exploring the complex mechanism of fatigue based on the ceRNA regulatory network is of great significance. In this review, we summarize the relationship between miRNAs, lncRNAs and circRNAs in ncRNAs and fatigue, and focus on exploring the regulatory role of the miRNA-centered ceRNA regulatory network in the occurrence and development of fatigue, in order to gain a comprehensive, in-depth and new understanding of the essence of the fatigue gene regulatory network.


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