Multiple RNA polymerases (RNAPs) transcribing a gene have been known to exhibit collective group behavior, causing the transcription elongation rate to increase with the rate of transcription initiation. Such behavior has long been believed to be driven by a physical interaction or "push" between closely spaced RNAPs. However, recent studies have posited that RNAPs separated by longer distances may cooperate via the DNA segment under transcription. Here, we present a theoretical model incorporating the mechanical coupling between RNAP translocation and the torsional response of supercoiled DNA. Using stochastic simulations, we demonstrate long-range cooperation between co-transcribing RNAPs mediated by DNA supercoiling. We find that inhibiting transcription initiation can slow down the already recruited RNAPs, in agreement with recent experimental observations, and predict that the average transcription elongation rate varies non-monotonically with the rate of transcription initiation. We further show that while RNAPs transcribing neighboring genes oriented in tandem can cooperate, those transcribing genes in divergent or convergent orientations can act antagonistically, and that such behavior holds over a large range of intergenic separations. Our model makes testable predictions, revealing how the mechanical interplay between RNAPs and the DNA they transcribe can govern a key cellular process.

中文翻译：

---

DNA超螺旋介导的共转录RNA聚合酶的集体行为

已知转录一个基因的多种RNA聚合酶（RNAP）表现出集体的群体行为，导致转录伸长率随转录起始速率的增加而增加。长期以来，人们一直认为这种行为是由间隔紧密的RNAP之间的物理相互作用或“推动”驱动的。但是，最近的研究表明，距离较远的RNAP可能通过转录下的DNA片段协同作用。在这里，我们提出了一个理论模型，其中包含了RNAP易位与超螺旋DNA扭转响应之间的机械耦合。使用随机模拟，我们证明了DNA超螺旋介导的共转录RNAP之间的远程合作。我们发现抑制转录启动可以减慢已经募集的RNAP，与最近的实验观察结果一致，并预测平均转录伸长率随转录起始速率非单调变化。我们进一步表明，虽然转录串联定向的相邻基因的RNAP可以协同作用，但转录方向不同或趋同的那些转录基因可以起拮抗作用，并且这种行为在大范围的基因间分离中保持。我们的模型做出了可检验的预测，揭示了RNAP和转录的DNA之间的机械相互作用如何控制关键的细胞过程。那些以不同或会聚方向转录的基因可以起拮抗作用，并且这种行为在大范围的基因间分离中起作用。我们的模型做出了可检验的预测，揭示了RNAP和转录的DNA之间的机械相互作用如何控制关键的细胞过程。那些以不同或会聚方向转录的基因可以起拮抗作用，并且这种行为在大范围的基因间分离中起作用。我们的模型做出了可检验的预测，揭示了RNAP和转录的DNA之间的机械相互作用如何控制关键的细胞过程。