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Effect of transcription reinitiation in stochastic gene expression
Journal of Statistical Mechanics: Theory and Experiment ( IF 2.4 ) Pub Date : 2021-03-09 , DOI: 10.1088/1742-5468/abdeb1
Rajesh Karmakar 1 , Amit Kumar Das 2
Affiliation  

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 GE 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 GE 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.



中文翻译:

转录重新初始化对随机基因表达的影响

基因表达(GE)是天生的随机或随机或嘈杂的过程。GE不同步骤(例如转录,翻译,降解等)中的随机性,导致mRNA和蛋白质水平的细胞间差异。这种变化出现在从微生物到后生动物的生物中。随机GE对细胞功能有重要影响。蛋白质水平的随机波动会导致细胞行为发生变化。它在某些情况下是有益的,而在其他情况下则是有害的。这些情况包括应激反应,新陈代谢,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,揭示了mRNA和蛋白质水平的波动是由GE的不同步骤引起的,其中转录步骤具有最大的作用。通过基于RNAP-II的转录重新启动产生搏动性mRNA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。在本构或两态过程中添加任何生化步骤通常会降低均值并增加Fano因子。在这项研究中,我们已经表明,在不同模型系统中,基于RNAP-II的基因转录重新初始化过程可能对均值和Fano因子的mRNA水平产生不同的影响。它在组成性网络的mRNA水平上均降低了均值和Fano因子,而在其他网络中,它可以同时增加或减少这两个数量,或者在mRNA水平上可能具有混合效应。

更新日期:2021-03-09
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