Processivity and coupling in messenger RNA transcription.
Processivity and coupling in messenger RNA transcription.
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DOI：
10.1371/journal.pone.0008845
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发表时间：
2010-01-28
期刊：
影响因子：
3.7
通讯作者：
Beggs JD
中科院分区：
文献类型：
--
作者：
Aitken S;Robert MC;Alexander RD;Goryanin I;Bertrand E;Beggs JD
信使RNA加工的复杂性现在正在通过能够检测细胞中mRNA的单个拷贝的实验技术和揭示动力学的定量实时观察来揭示。这种加工通常通过仅当启动子处于开启状态时才允许mRNA转录来模拟。在这个简单的开/关模型中，参与主动转录的许多过程由单个反应表示。这些过程包括伸长，其具有最短的完成时间和未在模型中捕获的处理时间。在本文中，我们更详细地探讨了代表延伸过程对mRNA分布的影响。延伸的机制的考虑导致两个替代模型之间的耦合延伸聚合酶和启动子的状态：持续加工性允许聚合酶完成延伸，而启动子的状态，而耦合需要启动子是活跃的，以产生全长转录。我们证明，这些替代品有一个显着的影响，预测的分布。用吉莱斯皮算法模拟模型，计算所得分布的三阶和四阶矩，以确定尾部的长度和峰的尖锐度。通过这种方法，我们表明，矩提供了一个简明的分布摘要，显示在大部分可行的参数范围内的显著差异。我们的结论是，持续合成能力是不完全一致的开/关模型，除非成功完成伸长的概率低，已经观察到。研究结果还表明，启动子和转录限速步骤之间的某种形式的耦合可能解释了细胞在低噪声下无法维持高mRNA水平的原因--这是一个没有支持证据的开/关模型预测。
The complexity of messenger RNA processing is now being uncovered by experimental techniques that are capable of detecting individual copies of mRNA in cells, and by quantitative real-time observations that reveal the kinetics. This processing is commonly modelled by permitting mRNA to be transcribed only when the promoter is in the on state. In this simple on/off model, the many processes involved in active transcription are represented by a single reaction. These processes include elongation, which has a minimum time for completion and processing that is not captured in the model. In this paper, we explore the impact on the mRNA distribution of representing the elongation process in more detail. Consideration of the mechanisms of elongation leads to two alternative models of the coupling between the elongating polymerase and the state of the promoter: Processivity allows polymerases to complete elongation irrespective of the promoter state, whereas coupling requires the promoter to be active to produce a full-length transcript. We demonstrate that these alternatives have a significant impact on the predicted distributions. Models are simulated by the Gillespie algorithm, and the third and fourth moments of the resulting distribution are computed in order to characterise the length of the tail, and sharpness of the peak. By this methodology, we show that the moments provide a concise summary of the distribution, showing statistically-significant differences across much of the feasible parameter range. We conclude that processivity is not fully consistent with the on/off model unless the probability of successfully completing elongation is low—as has been observed. The results also suggest that some form of coupling between the promoter and a rate-limiting step in transcription may explain the cell's inability to maintain high mRNA levels at low noise—a prediction of the on/off model that has no supporting evidence.