LncRNA 顺式与反式调控基因表达的差异分析

Differential Analysis of Cis-and Trans-Regulation of Gene Expression by LncRNA

研究表明长链非编码RNA (lncRNA) 在多个层面上参与重要生命过程的调控。然而迄今为止, lncRNA调控基因表达的机制复杂性及其生物学功能尚未完全阐明。本论文主要针对lncRNA通过顺式和反式两种方式调控基因表达的差异及其动态行为开展研究: 一、基于化学主方程建立lncRNA功能作用的数学模型并验证明了SSA和FSP算法的准确性; 二、利用SSA和FSP算法分析lncRNA分布及转录爆发对基因表达的影响。本文结合动力系统理论和随机模拟方法, 首先构建基于实验结果的lncRNA调控机制模型; 然后通过计算模型的一些关键指标 (如mRNA的概率分布、均值和噪声等) , 分析lncRNA在顺式与反式调控中表现出的动态特性。研究表明原始模型下的反式调控的mRNA表达量更高且噪声更低, 而顺式调控对快速局部响应更加敏感, 还研究了lncRNA生成分布对mRNA表达的动态特性的影响, 发现不同分布形式显著影响调控模式的稳定性和表达效率。同时加入转录爆发后, 相比反式调控, 顺式调控mRNA的表达平均量更高且噪声更低。本研究为全面理解lncRNA的调控机制及其在基因表达中的功能特性提供了理论支持, 为探索lncRNA调控机制提供了新视角。

Research has shown that long non-coding RNAs (lncRNAs) are involved in the regulation of essential biological processes at multiple levels. However so far, the mechanisms of gene expression regulation by lncRNAs and their biological functions are not yet fully understood. This study focuses on the differences in gene expression regulation by lncRNAs through cis-and trans-regulation and their dynamic behaviors. First, a mathematical model for the functional action of lncRNAs is established based on chemical master equations, and the accuracy of the SSA and FSP algorithms is validated. Second, the distribution of lncRNAs and the effect of transcriptional bursts on gene expression are analyzed using SSA and FSP algorithms. This paper combines dynamical system theory and stochastic simulation methods to first construct the model of lncRNA regulatory mechanisms based on experimental results; Then some key indicators ( such as the probability distribution, mean, and noise of mRNA) are then calculated to analyze the dynamic properties exhibited by lncRNAs in cis-and trans-regulation. The study shows that under the original model, trans-regulation leads to higher mRNA expression levels and lower noise, while cis-regulation is more sensitive to rapid local responses. The impact of the lncRNA generation distribution on the dynamic characteristics of mRNA expression is also studied, and it is found that different distribution forms significantly affect the stability and efficiency of the regulatory pattern. After adding transcriptional bursts, cisregulation results in higher average mRNA expression levels and lower noise compared to trans-regulation. This study provides theoretical support for a comprehensive understanding of lncRNA regulatory mechanisms and their functional characteristics in gene expression, offering a new perspective for exploring lncRNA regulatory mechanisms.