Bistability in gene transcription: Interplay of messenger RNA, protein, and nonprotein coding RNA

The author proposes a kinetic model describing the interplay of messenger ribonucleic acid (mRNA), protein, produced via translation of this RNA, and nonprotein coding RNA (ncRNA). The model includes association of mRNA and ncRNA and regulation of the ncRNA production by protein. In the case of positive feedback between the production of protein and ncRNA, the steady state of the system is found to be unique. For negative feedback, the model predicts in the mean-field case either unique steady state or bistable kinetics. With incorporation of fluctuations, the bistability is manifested in the form of kinetic bursts provided that the number of reactants is low. Basically, the model describes the simplest biological switch operating with participation of ncRNA. Although the results obtained are applicable to ncRNSs in general, the presentation is focused primarily on microRNAs (miRNAs) which form a large important subclass of ncRNAs and are thought to regulate up to one third of all human genes.