Ribosome reactivates transcription by physically pushing RNA polymerase out of transcription arrest.
Ribosome reactivates transcription by physically pushing RNA polymerase out of transcription arrest.
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DOI：
10.1073/pnas.1919985117
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发表时间：
2020-04-14
影响因子：
11.1
通讯作者：
Zenkin, Nikolay
中科院分区：
文献类型：
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作者：
Stevenson-Jones, Flint;Woodgate, Jason;Zenkin, Nikolay
在细菌中，基因表达的前两个步骤转录和终止在空间和时间上是相互耦合的。解偶联可能导致通过RNA聚合酶回溯的转录停滞，其干扰复制叉，导致DNA双链断裂和基因组不稳定。转录-翻译偶联如何缓解这些冲突尚不清楚。在这里，我们表明，与复制，翻译不受抑制逮捕转录延伸复合物。相反，翻译核糖体主动将RNA聚合酶从回溯状态推出来，从而重新激活转录。我们发现，这两种机器在mRNA上接触时的距离比以前认为的要小，这表明它们之间存在密切的相互作用。然而，这并不像曾经提出的那样导致酶之间形成稳定的功能复合物。我们的研究结果揭示了一个积极的，能量驱动的机制，重新激活回溯延伸复合物，从而有助于抑制它们的干扰复制。
In bacteria, the first two steps of gene expression-transcription and translation-are spatially and temporally coupled. Uncoupling may lead to the arrest of transcription through RNA polymerase backtracking, which interferes with replication forks, leading to DNA double-stranded breaks and genomic instability. How transcription-translation coupling mitigates these conflicts is unknown. Here we show that, unlike replication, translation is not inhibited by arrested transcription elongation complexes. Instead, the translating ribosome actively pushes RNA polymerase out of the backtracked state, thereby reactivating transcription. We show that the distance between the two machineries upon their contact on mRNA is smaller than previously thought, suggesting intimate interactions between them. However, this does not lead to the formation of a stable functional complex between the enzymes, as was once proposed. Our results reveal an active, energy-driven mechanism that reactivates backtracked elongation complexes and thus helps suppress their interference with replication.