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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Phosphorylation of the RNA polymerase II C-terminal domain by TFIIH kinase is not essential for transcription of Saccharomyces cerevisiae genome
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Phosphorylation of the RNA polymerase II C-terminal domain by TFIIH kinase is not essential for transcription of Saccharomyces cerevisiae genome

机译:TFIIH激酶对RNA聚合酶II C末端结构域的磷酸化对于酿酒酵母基因组的转录不是必需的

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摘要

Ser-5 phosphorylation of the RNA polymerase II (Pol II) C-terminal domain by TFIIH kinase has been implicated in critical steps in mRNA synthesis, such as Pol II promoter escape and mRNA 5'-capping. However, the general requirement and precise role of TFIIH kinase in Pol II transcription still remain elusive. Here we use a chemical genetics approach to show that, for a majority of budding-yeast genes, specific inhibition of the yeast TFIIH kinase results in a dramatic reduction in both mRNA level and Ser-5 C-terminal domain phosphorylation. Surprisingly, inhibition of TFIIH kinase activity only partially affected both Pol II density and Ser-2 phosphorylation level. The discrepancy between mRNA level and Pol II density is attributed to the defective 5-capping, which results in the destabilization of mRNAs. Therefore, contrary to the current belief, our study points strongly toward a minor role of TFIIH kinase in Pol II transcription, and a more significant role in mRNA capping in budding yeast.
机译:TFIIH激酶使RNA聚合酶II(Pol II)C末端结构域的Ser-5磷酸化参与了mRNA合成的关键步骤,例如Pol II启动子逃逸和mRNA 5'封闭。但是,TFIIH激酶在Pol II转录中的一般要求和确切作用仍然难以捉摸。在这里,我们使用化学遗传学方法显示,对于大多数发芽酵母基因,酵母TFIIH激酶的特异性抑制导致mRNA水平和Ser-5 C末端域磷酸化的急剧降低。令人惊讶地,TFIIH激酶活性的抑制仅部分影响Pol II密度和Ser-2磷酸化水平。 mRNA水平和Pol II密度之间的差异归因于有缺陷的5上限,这导致mRNA不稳定。因此,与当前的观点相反,我们的研究强烈指向TFIIH激酶在Pol II转录中的次要作用,而在发芽酵母中的mRNA上限中则起着更重要的作用。

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    Global Research Laboratory for RNAi Medicine and Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea BK21 School of Chemical Materials Science and Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea;

    Global Research Laboratory for RNAi Medicine and Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea;

    Global Research Laboratory for RNAi Medicine and Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea BK21 School of Chemical Materials Science and Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea;

    Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757, Korea;

    Department of Biomedical Engineering, Dongguk University, Seoul 100-715, Korea;

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853;

    Global Research Laboratory for RNAi Medicine and Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea BK21 School of Chemical Materials Science and Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Korea;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    chemical genetics; Kin28; mRNA capping;

    机译:化学遗传学Kin28;mRNA封端;

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