The mechanisms underlying the initiation and elongation of RNA polymerase II (Pol II) transcription are well-studied, whereas termination remains poorly understood. Here we analyze the mechanism of polyadenylation-independent Pol II termination mediated by the yeast Sen1 helicase. Cryo-electron microscopy structures of two pretermination intermediates show that Sen1 binds to Pol II and uses its adenosine triphosphatase activity to pull on exiting RNA in the 5′ direction. This is predicted to push Pol II forward, induce an unstable hypertranslocated state and destabilize the transcription bubble, thereby facilitating termination. This mechanism of transcription termination may be widely used because it is conceptually conserved in the bacterial transcription system.

RNA 聚合酶 II （Pol II） 转录起始和延伸的潜在机制已得到充分研究，而终止仍然知之甚少。在这里，我们分析了酵母 Sen1 解旋酶介导的不依赖聚腺苷酸化的 Pol II 终止的机制。两种预终止中间体的冷冻电子显微镜结构显示，Sen1 与 Pol II 结合，并利用其腺苷三磷酸酶活性沿 5' 方向拉动退出的 RNA。预计这会推动 Pol II 向前发展，诱导不稳定的超易位状态并破坏转录气泡的稳定性，从而促进终止。这种转录终止机制可能被广泛使用，因为它在细菌转录系统中在概念上是保守的。