The RNA polymerase II largest subunit C-terminal domain consists of repeated YSPTSPS heptapeptides. The role of tyrosine-1 (Tyr1) remains incompletely understood, as, for example, mutating all Tyr1 residues to Phe (Y1F) is lethal in vertebrates but a related mutant has only a mild phenotype in S. pombe. Here we show that Y1F substitution in budding yeast resulted in a strong slow-growth phenotype. The Y1F strain was also hypersensitive to several different cellular stresses that involve MAP kinase signaling. These phenotypes were all linked to transcriptional changes, and we also identified genetic and biochemical interactions between Tyr1 and both transcription initiation and termination factors. Further studies uncovered defects related to MAP kinase I (Slt2) pathways, and we provide evidence that Slt2 phosphorylates Tyr1 in vitro and in vivo. Our study has thus identified Slt2 as a Tyr1 kinase, and in doing so provided links between stress response activation and Tyr1 phosphorylation.

RNA聚合酶II最大的亚基C末端结构域由重复的YSPTSPS七肽组成。酪氨酸-1（Tyr1）的作用仍未完全了解，例如，在脊椎动物中将所有Tyr1残基突变为Phe（Y1F）是致命的，但相关突变体在粟酒裂殖酵母中仅具有轻度表型。。在这里，我们显示出发芽酵母中的Y1F替代导致了一个强的慢速生长表型。Y1F菌株对涉及MAP激酶信号传导的几种不同细胞应激也非常敏感。这些表型都与转录变化有关，我们还鉴定了Tyr1与转录起始和终止因子之间的遗传和生化相互作用。进一步的研究发现了与MAP激酶I（Slt2）途径相关的缺陷，我们提供了Slt2在体外和体内磷酸化Tyr1的证据。因此，我们的研究已将Slt2鉴定为Tyr1激酶，并在此过程中提供了应激反应激活与Tyr1磷酸化之间的联系。