RNA polymerase II (RNA Pol II) contains a disordered C-terminal domain (CTD) whose length enigmatically correlates with genome size. The CTD is crucial to eukaryotic transcription, yet the functional and evolutionary relevance of this variation remains unclear. Here, we investigate how CTD length and disorder influence transcription. We find that length modulates the size and frequency of transcriptional bursting. Disorder is highly conserved and facilitates CTD-CTD interactions, an ability we show is separable from protein sequence and necessary for efficient transcription. We build a data-driven quantitative model, simulations of which recapitulate experiments and support that CTD length promotes initial polymerase recruitment to the promoter and slows down its release from it and that CTD-CTD interactions enable recruitment of multiple polymerases. Our results reveal how these parameters provide access to a range of transcriptional activity, offering a new perspective for the mechanistic significance of CTD length and disorder in transcription across eukaryotes.

RNA聚合酶II（RNA Pol II）包含一个无序的C末端结构域（CTD），其长度与基因组大小神秘地相关。CTD对真核转录至关重要，但这种变异的功能和进化相关性仍不清楚。在这里，我们调查CTD长度和疾病如何影响转录。我们发现长度调节转录突发的大小和频率。疾病高度保守并促进CTD-CTD相互作用，我们显示的能力与蛋白质序列是分离的，并且是有效转录所必需的。我们建立了一个数据驱动的量化模型，模拟过程概括了实验，并支持CTD的长度促进了初始聚合酶向启动子的募集并减慢了从启动子的释放，并且CTD-CTD相互作用使得可以募集多种聚合酶。我们的结果揭示了这些参数如何提供对一系列转录活性的访问，为跨真核生物的CTD长度和转录失序的机械意义提供了新的观点。