The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is composed of a repetition of YSPTSPS heptads and functions as a loading platform for protein complexes that regulate transcription, splicing, and maturation of RNAs. Here, we studied mammalian CTD mutants to analyze the function of tyrosine1 residues in the transcription cycle. Mutation of 3/4 of the tyrosine residues (YFFF mutant) resulted in a massive read-through transcription phenotype in the antisense direction of promoters as well as in the 3′ direction several hundred kilobases downstream of genes. The YFFF mutant shows reduced Pol II at promoter-proximal pause sites, a loss of interaction with the Mediator and Integrator complexes, and impaired recruitment of these complexes to chromatin. Consistent with these observations, Pol II loading at enhancers and maturation of snRNAs are altered in the YFFF context genome-wide. We conclude that tyrosine1 residues of the CTD control termination of transcription by Pol II.

RNA聚合酶（Pol）II的羧基末端结构域（CTD）由YSPTSPS七肽的重复组成，并充当调节RNA转录，剪接和成熟的蛋白质复合物的加载平台。在这里，我们研究了哺乳动物的CTD突变体，以分析酪氨酸1残基在转录周期中的功能。3/4的酪氨酸残基的突变（YFFF突变体）在启动子的反义方向以及在基因下游的几百千个碱基的3'方向上产生了大量的通读转录表型。YFFF突变体显示启动子近端停顿位点的Pol II减少，与介体和整合子复合物的相互作用丧失，以及这些复合物向染色质的募集受损。与这些观察结果一致，在全基因组的YFFF环境中，增强子上的Pol II加载和snRNA的成熟发生了变化。我们得出结论，CTD的酪氨酸1残基控制Pol II转录的终止。