论文标题
随机基因表达中转录重新定量的影响
Effect of transcription reinitiation in stochastic gene expression
论文作者
论文摘要
基因表达(GE)是固有的随机或随机或嘈杂的过程。 GE的不同步骤中的随机性,例如转录,翻译,降解等,导致细胞间mRNA和蛋白质水平的变化。这种变异出现在从微生物到后生动物的生物体中。随机基因表达对细胞功能具有重要的后果。蛋白质水平的随机波动会导致细胞行为的变化。它在某些情况下是有益的,对其他情况有害。这些情况包括压力反应,代谢,发育,细胞周期,昼夜节律和衰老。不同的模型研究,例如本构,两态等,表明mRNA和蛋白质水平的波动来自基因表达的不同步骤,其中转录步骤具有最大效果。通过基于RNAP-II的转录重新定量的脉冲mRNA产生是基因转录的重要组成部分。但是,该过程对mRNA和蛋白质水平的影响鲜为人知。在本构或两国过程中,任何生化步骤的添加通常会降低平均值并增加FANO因子。在这项研究中,我们已经表明,基因转录中的基于RNAP-II的重新定性过程对不同模型系统中mRNA水平的均值和Fano因子都有不同的影响。它降低了本构网络中mRNA水平的平均值和FANO因子,而在其他网络中,它可以同时增加或减少这两个量,或者在mRNA水平下可能具有混合效应。我们建议具有重新激活的组成型网络的行为就像是产品独立的负反馈电路,而其他网络则作为产品独立的正面或负反馈电路的行为。
Gene expression (GE) is an inherently random or stochastic or noisy process. The randomness in different steps of GE, e.g., transcription, translation, degradation, etc., leading to cell-to-cell variations in mRNA and protein levels. This variation appears in organisms ranging from microbes to metazoans. Stochastic gene expression has important consequences for cellular function. The random fluctuations in protein levels produce variability in cellular behavior. It is beneficial in some contexts and harmful to others. These situations include stress response, metabolism, development, cell cycle, circadian rhythms, and aging. Different model studies e.g., constitutive, two-state, etc., reveal that the fluctuations in mRNA and protein levels arise from different steps of gene expression among which the steps in transcription have the maximum effect. The pulsatile mRNA production through RNAP-II based reinitiation of transcription is an important part of gene transcription. Though, the effect of that process on mRNA and protein levels is very little known. The addition of any biochemical step in the constitutive or two-state process generally decreases the mean and increases the Fano factor. In this study, we have shown that the RNAP-II based reinitiation process in gene transcription can have different effects on both mean and Fano factor at mRNA levels in different model systems. It decreases the mean and Fano factor both at the mRNA levels in the constitutive network whereas in other networks it can simultaneously increase or decrease both quantities or it can have mixed-effect at mRNA levels. We propose that a constitutive network with reinitiation behaves like a product independent negative feedback circuit whereas other networks behave as either product independent positive or negative or mixed feedback circuit.