School of Mathematics Science, Tianjin Normal University, Tianjin 300387, China.
School of Mathematics and Systems Science and LMIB, Beihang University, Beijing 100191, China.
Neural Plast. 2021 Mar 25;2021:6668389. doi: 10.1155/2021/6668389. eCollection 2021.
Noncoding RNAs such as miRNAs and piRNAs have long-lasting effects on the regulation of gene expression involved in long-term synaptic changes. To characterize gene regulation mediated by small noncoding RNAs associated with long-term memory in , we consider two noncoding RNAs stimulated by 5-HT into a gene regulatory network motif model, including miR-124 that binds to and inhibits the mRNA of CREB1 and piR-F that facilitates serotonin-dependent DNA methylation to lead to repression of CREB2. Codimension-1 and -2 bifurcation analyses of 5-HT regulating both miR-124 and piR-F and a negative feedback strength for oscillation reveal rich dynamical properties of bistability and oscillations robust to variations in all other parameters. More importantly, we verify three stimulus protocols of 5-HT in experiments by our model and find that application of five pulses of 5-HT leads to a transient decrease of miR-124 but increase of piR-F concentrations, which matters sustained high level of CREB1 concentration associated with long-term memory. Furthermore, we perform bifurcation analyses for the concentrations of miR-124 and piR-F as two parameters to explore dynamical mechanisms underlying the epigenetic regulation in long-term memory formation. This study provides insights into revealing regulatory roles of epigenetic changes in gene expression involving noncoding RNAs associated with synaptic plasticity.
非编码 RNA 如 miRNA 和 piRNA 对参与长期突触变化的基因表达调控具有持久影响。为了描述与长期记忆相关的小非编码 RNA 介导的基因调控，我们考虑了两种受 5-HT 刺激的非编码 RNA，将其纳入基因调控网络基模模型，包括结合并抑制 CREB1 mRNA 的 miR-124 和促进与 5-HT 相关的 DNA 甲基化以抑制 CREB2 的 piR-F。5-HT 调节 miR-124 和 piR-F 以及负反馈强度的二维和一维分岔分析揭示了双稳和振荡的丰富动力学特性，对所有其他参数的变化具有鲁棒性。更重要的是，我们通过模型验证了实验中的三种 5-HT 刺激方案，发现施加五个脉冲的 5-HT 会导致 miR-124 浓度短暂下降但 piR-F 浓度增加，这与与长期记忆相关的 CREB1 浓度的持续高水平有关。此外，我们将 miR-124 和 piR-F 的浓度作为两个参数进行分岔分析，以探讨长期记忆形成中表观遗传调控的动力学机制。本研究为揭示与突触可塑性相关的非编码 RNA 参与的基因表达的表观遗传调控的调节作用提供了深入了解。
