Single cell experiments of simple regulatory networks can markedly differ from cell population experiments. Such differences arise from stochastic events in individual cells that are averaged out in cell populations. For instance, while individual cells may show sustained oscillations in the concentrations of some proteins, such oscillations may appear damped in the population average. In this paper we investigate the role of RNA stochastic fluctuations as a leading force to produce a sustained excitatory behavior at the single cell level. Opposed to some previous models, we build a fully stochastic model of a negative feedback loop that explicitly takes into account the RNA stochastic dynamics. We find that messenger RNA random fluctuations can be amplified during translation and produce sustained pulses of protein expression. Motivated by the recent appreciation of the importance of non--coding regulatory RNAs in post--transcription regulation, we also consider the possibility that a regulatory RNA transcript could bind to the messenger RNA and repress translation. Our findings show that the regulatory transcript helps reduce gene expression variability both at the single cell level and at the cell population level.
Computational prediction of RNA tertiary structures using machine learning methods
National Laboratory of Solid State Microstructures（固体微结构国家实验室）；School of Physics（物理学院）；Collaborative Innovation Center of Advanced Microstructures（先进微结构协同创新中心）；Nanjing University（南京大学）；Institute for Brain Sciences（脑科学研究院）；Kuang Yaming Honors School（匡亚明学院）
Competing endogenous RNA crosstalk at system level
microRNAs（miRNAs）通过抑制靶RNA分子在转录后水平调控基因表达。竞争结合miRNA往往反过来关联它们的靶标，建立有效的RNA-RNA相互作用，可以影响表达水平，缓冲波动并促进信号传播。这样的潜力已经在数学上表征为小图案在稳态和\red{away from stationarity}。另一方面，实验证据表明竞争性内源RNA（ceRNA）串扰相当弱。然而，扩展的miRNA-RNA网络可能有利于许多串扰相互作用的整合，导致显著的大规模效应，尽管单个链接的弱点。为了阐明串扰在多大程度上是由miRNA相互作用组维持的，我们在大规模的miRNA-RNA网络重建中研究了其涌现的系统特征。我们表明，虽然一般弱，系统水平的串扰模式（i）增强了转录异质性，（ii）可以实现高强度，甚至对于RNA，不共调节，（iii）是强大的转录速率的变化，和（iv）是显着的非本地，即弱相关的miRNA-RNA相互作用参数。此外，当串扰最强时，RNA水平一般更稳定。由于这些特征中的一些似乎被编码在网络的拓扑结构中，串扰可能在功能上受到自然选择的青睐。这些结果表明，除了它们的抑制作用外，miRNA还介导了一个弱但有弹性且与上下文无关的交叉调节相互作用网络，该网络将转录组互连，稳定表达水平并支持系统水平的反应。
