3-Econsystems: MicroRNAs, Receptors, and Latent Viruses; Some Insights Biology Can Gain from Economic Theory

Abstract

This mini-review describes three biological systems. All three include competing molecules and a limiting molecule that binds the competing molecules. Such systems are extensively researched by economists. In fact, the issue of limited resources is the defining feature of economic systems. Therefore, we call these systems "econsystems." In an econsystem, the allocation of the limiting molecule between the competing molecules determines the behavior of the system. A cell is an example of an econsystem. Therefore, a change in the allocation of a limiting molecule as a result of, for instance, an abnormal change in the concentration of one of the competing molecules, may result in abnormal cellular behavior, and disease. The first econsystem described in this mini-review includes a long non-coding RNA and a messenger RNA (lncRNA and mRNA). The limiting molecule is a microRNA (miRNA). The lncRNA and mRNA are known as competing endogenous RNAs (ceRNAs). The second econsystem includes two receptors, and the limiting molecule is a ligand. The third econsystem includes a cis-regulatory element of a latent virus and that of a human gene. The limiting molecule is a transcription complex that binds both cis-elements.

Keywords: GA-binding protein; cis-regulatory element; latent virus; long non-coding RNA; microRNA; microcompetition.

Figure 1

(A) Both mRNA and lncRNA have miRNA binding sites (miRNA response elements, or MRE), which bind miRNA. Since the concentration of miRNA is limiting, the lncRNA decreases the availability of the miRNA to mRNA. (B) Residence Time. When observing the behavior of a ligand, L, for 10 min, (i) in the presence of R₁ only, the observer sees L bound to the receptor 10% of the time (i.e., 1 min). (ii) When observing the behavior of L in the presence of both R₁ and R₂, where R₂ has 2 times more affinity for the ligand L than does R₁, the residence time on R₂ is 2 min, and the residence time on R₁ is 0.8 min (10% of the time L is free, that is, 8 min). (iii) Consider R₃ that has a 5 times higher affinity relative to R₁. When observing the behavior of L in the presence of both R₁ and R₃, the residence time of R₃ is 5 min. The residence time of R₁ is, therefore, 10% of the time L is free, or unbound, that is, 10% of 5 min, or 0.5 min. (C) An increase in latent viral copy number leads to a decrease in GABP•p300 availability to the cellular gene promoter (note the pink arrow). The result is a dysregulation in cellular gene expression.

Figure 2

(A) The chart above displays the relationship between binding affinity and residence time. The x-axis represents the binding affinity of a receptor, when this affinity is measured without the presence of R₁. The y-axis represents the residence time of the ligand on R₁. The first data point represents the residence time of L on R₁ with no competitive receptors. The second data point represents the residence time of L on R₁ when both R₂ and R₁ are present, and R₂ has double the affinity of R₁. The third data point represents the residence time of L on R₁ when both R₃ and R₁ are present, and R₃ has 5-times the affinity of R₁. As the binding affinity of the competing receptor increases, the residence time of L on R₁ decreases. (B) Liu et al. reports the expression level driven by the CMV enhancer/promoter (measured in relative light units, or RLU) vs. those driven by the PDGF-b promoter in a variety of cells. Based on the numbers on the y-axis, which are depicted logarithmically, suggests that the CMV P/E is about 150-fold stronger than the PDGF-b promoter.