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Multiple Roles for the Ess1 Prolyl Isomerase in the RNA Polymerase II Transcription Cycle

机译：Ess1脯氨酰异构酶在RNA聚合酶II转录周期中的多重作用。

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摘要

The Ess1 prolyl isomerase in Saccharomyces cerevisiae regulates RNA polymerase II (pol II) by isomerizing peptide bonds within the pol II carboxy-terminal domain (CTD) heptapeptide repeat (YSPTSPS). Ess1 preferentially targets the Ser5-Pro6 bond when Ser5 is phosphorylated. Conformational changes in the CTD induced by Ess1 control the recruitment of essential cofactors to the pol II complex and may facilitate the ordered transition between initiation, elongation, termination, and RNA processing. Here, we show that Ess1 associates with the phospho-Ser5 form of polymerase in vivo, is present along the entire length of coding genes, and is critical for regulating the phosphorylation of Ser7 within the CTD. In addition, Ess1 represses the initiation of cryptic unstable transcripts (CUTs) and is required for efficient termination of mRNA transcription. Analysis using strains lacking nonsense-mediated decay suggests that as many as half of all yeast genes depend on Ess1 for efficient termination. Finally, we show that Ess1 is required for trimethylation of histone H3 lysine 4 (H3K4). Thus, Ess1 has direct effects on RNA polymerase transcription by controlling cofactor binding via conformationally induced changes in the CTD and indirect effects by influencing chromatin modification.
机译：酿酒酵母中的Ess1脯氨酰异构酶通过使pol II羧基末端域（CTD）七肽重复序列（YSPTSPS）中的肽键异构化来调节RNA聚合酶II（pol II）。当Ser5磷酸化时，Ess1优先靶向Ser5-Pro6键。由Ess1诱导的CTD的构象变化控制着必需辅因子向pol II复合体的募集，并可能促进起始，延伸，终止和RNA处理之间的有序过渡。在这里，我们显示Ess1与体内聚合酶磷酸化Ser5形式相关，在编码基因的整个长度上均存在，并且对于调节CTD中Ser7的磷酸化至关重要。此外，Ess1抑制隐性不稳定转录本（CUT）的启动，是有效终止mRNA转录所必需的。使用缺乏无意义介导的衰变的菌株进行的分析表明，所有酵母基因中多达一半依赖Ess1进行有效终止。最后，我们显示Ess1是组蛋白H3赖氨酸4（H3K4）的三甲基化所必需的。因此，Ess1通过构象诱导的CTD变化控制辅因子结合，直接影响RNA聚合酶转录，而通过影响染色质修饰则具有间接作用。

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