The Origin of Short Transcriptional Pauses
The Origin of Short Transcriptional Pauses
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DOI：
10.1016/j.bpj.2008.12.3918
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发表时间：
2009-03-18
影响因子：
3.4
通讯作者：
Grill, Stephan W.
中科院分区：
文献类型：
--
作者：
Depken, Martin;Galburt, Eric A.;Grill, Stephan W.
RNA 聚合酶是将遗传信息从 DNA 转录为 RNA 的蛋白质分子机器。 RNA 分子的延伸经常被停顿打断，其具体性质仍然存在争议。在这里，我们要问的是，回溯（长暂停背后的核心机制）是否也可能导致通常归因于普遍暂停状态的短暂停。为此，我们将回溯建模为偏向力的随机游走，从而产生实验中观察到的暂停持续时间的广泛分布。重要的是，我们发现这种单一机制自然地产生了两种在持续时间和轨迹上都不同的停顿群体：具有扩散回溯预期行为的长时间停顿，以及具有与普遍存在的停顿类似特征的新型短时回溯。这些特征包括聚合酶的明显的力不敏感性和固定性。根据这些结果以及与已发表的用光镊测量的暂停轨迹的定量比较，我们认为短暂停的很大一部分仅仅是由于回溯造成的。
RNA polymerases are protein molecular machines that transcribe genetic information from DNA into RNA. The elongation of the RNA molecule is frequently interrupted by pauses, the detailed nature of which remains controversial. Here we ask whether backtracking, the central mechanism behind long pauses, could also be responsible for short pauses normally attributed to the ubiquitous pause state. To this end, we model backtracking as a force-biased random walk, giving rise to a broad distribution of pause durations as observed in experiments. Importantly, we find that this single mechanism naturally generates two populations of pauses that are distinct both in duration and trajectory: long-time pauses with the expected behavior of diffusive backtracks, and a new class of short-time backtracks with characteristics similar to those of the ubiquitous pause. These characteristics include an apparent force insensitivity and immobility of the polymerase. Based on these results and a quantitative comparison to published pause trajectories measured with optical tweezers, we suggest that a significant fraction of short pauses are simply due to backtracking.