Mathematical Modeling for Oscillations Driven by Noncoding RNAs

Abstract

In this chapter, we first survey strategies for the mathematical modeling of gene regulatory networks for capturing physiologically important dynamics in cells such as oscillations. We focus on models based on ordinary differential equations with various forms of nonlinear functions that describe gene regulations. We next use a small system of a microRNA and its mRNA target to illustrate a recently discovered oscillator driven by noncoding RNAs. This oscillator has unique features that distinguish it from conventional biological oscillators, including the absence of an imposed negative feedback loop and the divergence of the periods. The latter property may serve crucial biological functions for restoring heterogeneity of cell populations on the timescale of days. We describe general requirements for obtaining the limit cycle oscillations in terms of underlying biochemical reactions and kinetic rate constants. We discuss future directions stemming from this minimal, noncoding RNA-based model for gene expression oscillation.

Keywords: Biochemical oscillator; Limit cycle; Mathematical modeling; Ordinary differential equation; microRNA.