A Unified Model of Transcription Elongation: What Have We Learned from Single-Molecule Experiments?
A Unified Model of Transcription Elongation: What Have We Learned from Single-Molecule Experiments?
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DOI：
10.1016/j.bpj.2010.12.3734
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发表时间：
2011-03-02
影响因子：
3.4
通讯作者：
Ruckenstein, Andrei E.
中科院分区：
文献类型：
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作者：
Maoileidigh, Daibhid O.;Tadigotla, Vasisht R.;Ruckenstein, Andrei E.
DNA中编码的遗传信息转录成RNA是由RNA聚合酶（RNAP）完成的，RNAP是一种复杂的分子马达，在物种间高度保守。尽管单分子技术的显着进步，揭示了重要的转录延伸（TE）与碱基对分辨率的机制细节，这些研究的一些结果和解释是难以调和的，并没有导致一个最小的统一的图片转录。我们提出了一个简单的模型，占定量的许多实验观察。该模型属于TE的等温棘轮模型类，涉及RNAP沿着DNA在单核苷酸掺入事件之间的热驱动随机向后和向前运动（回溯和向前追踪）。我们揭示了该模型成功的两个基本特征。第一个是中间状态，将生产性延伸途径与非延伸性回溯状态分开。进入和退出该中间状态的速率通过RNAP调节暂停。该模型的第二个关键成分是RNA转录物的共转录折叠，在空间上抑制回溯的程度。该模型解决了单分子研究之间的几个明显差异，并为TE的未来工作提供了一个框架。
The transcription of the genetic information encoded in DNA into RNA is performed by RNA polymerase (RNAP), a complex molecular motor, highly conserved across species. Despite remarkable progress in single-molecule techniques revealing important mechanistic details of transcription elongation (TE) with up to base-pair resolution, some of the results and interpretations of these studies are difficult to reconcile, and have not yet led to a minimal unified picture of transcription. We propose a simple model that accounts quantitatively for many of the experimental observations. This model belongs to the class of isothermal ratchet models of TE involving the thermally driven stochastic backward and forward motion (backtracking and forward tracking) of RNAP along DNA between single-nucleotide incorporation events. We uncover two essential features for the success of the model. The first is an intermediate state separating the productive elongation pathway from nonelongating backtracked states. The rates of entering and exiting this intermediate state modulate pausing by RNAP. The second crucial ingredient of the model is the cotranscriptional folding of the RNA transcript, sterically inhibiting the extent of backtracking. This model resolves several apparent differences between single-molecule studies and provides a framework for future work on TE.