Mechanisms generating bistability and oscillations in microRNA-mediated motifs

摘要: The importance of post-transcriptional regulation by microRNAs (miRNAs) has recently been recognized in almost all cellular processes. When participating processes, miRNAs mainly mediate mRNA degradation or translational repression. Recently computational and experimental studies have identified an abundance motifs involving transcriptional factors (TFs). simplest motif is a two-node miRNA-mediated feedback loop (MFL) which TF regulates miRNA the itself negatively regulated miRNA. In this paper we present general model for MFL based on biochemical regulations explore its dynamics using bifurcation analysis. Our results show that can behave either as switches oscillators, depending repressor activator. These functional features are consistent with widespread appearance fate decisions such proliferation, differentiation, apoptosis during development. We found under interplay miRNA, wide ranges parameters even without cooperative binding TF. addition, oscillations induced require neither additional positive loop, nor self-activation gene, TF, saturated degradation. Therefore, may provide network structure to induce bistability oscillations. It hoped presented here will new view how gene expression further guidance experiments. Moreover, insight gained from study also expected basis investigation more complex networks assembled simple building blocks.