Theoretical analysis of transcription process with polymerase stalling.
Theoretical analysis of transcription process with polymerase stalling.
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DOI：
10.1103/physreve.91.052713
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发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Jingwei Li;Yunxin Zhang
中科院分区：
文献类型：
--
作者：
Jingwei Li;Yunxin Zhang
实验证据表明，在基因转录中RNA聚合酶有可能被停在转录模板的某个位置。这可能是由于模板损伤或蛋白质屏障。一旦停止，聚合酶可能沿着模板回溯到先前的核苷酸，等待受损位点的修复，或者简单地绕过屏障或受损位点，从而合成错误的信使RNA，或者降解并脱离模板。因此，有效转录速率（合成正确产物mRNA的速率）和转录效率（有效转录速率与有效转录起始速率之比）都受到聚合酶停滞事件的影响。到目前为止，还没有理论模型来讨论包括聚合酶停滞在内的基因转录过程。本研究基于完全不对称的简单排斥过程，从理论上分析了包括聚合酶停滞在内的转录过程。详细讨论了有效转录率、有效转录起始率和转录有效性对转录起始率、终止率以及失速时的回溯率、绕过率和脱离（降解）率的依赖关系。结果表明，聚合酶失速后回溯重启是提高有效转录率和转录效率的理想机制。在不回溯的情况下，脱离停滞的聚合酶也有助于提高有效转录率和转录效率。一般来说，停滞聚合酶的旁路速率的增加会导致有效转录速率和转录效率的降低。然而，当停滞聚合酶的脱离率和回溯率消失时，有效转录率也可能通过旁路机制而增加。
Experimental evidence shows that in gene transcription RNA polymerase has the possibility to be stalled at a certain position of the transcription template. This may be due to the template damage or protein barriers. Once stalled, polymerase may backtrack along the template to the previous nucleotide to wait for the repair of the damaged site, simply bypass the barrier or damaged site and consequently synthesize an incorrect messenger RNA, or degrade and detach from the template. Thus, the effective transcription rate (the rate to synthesize correct product mRNA) and the transcription effectiveness (the ratio of the effective transcription rate to the effective transcription initiation rate) are both influenced by polymerase stalling events. So far, no theoretical model has been given to discuss the gene transcription process including polymerase stalling. In this study, based on the totally asymmetric simple exclusion process, the transcription process including polymerase stalling is analyzed theoretically. The dependence of the effective transcription rate, effective transcription initiation rate, and transcription effectiveness on the transcription initiation rate, termination rate, as well as the backtracking rate, bypass rate, and detachment (degradation) rate when stalling, are discussed in detail. The results showed that backtracking restart after polymerase stalling is an ideal mechanism to increase both the effective transcription rate and the transcription effectiveness. Without backtracking, detachment of stalled polymerase can also help to increase the effective transcription rate and transcription effectiveness. Generally, the increase of the bypass rate of the stalled polymerase will lead to the decrease of the effective transcription rate and transcription effectiveness. However, when both detachment rate and backtracking rate of the stalled polymerase vanish, the effective transcription rate may also be increased by the bypass mechanism.