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Tyrosine-1 of RNA Polymerase II CTD Controls Global Termination of Gene Transcription in Mammals

机译:RNA聚合酶II CTD的酪氨酸-1控制哺乳动物中的全球终止基因转录

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摘要

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 30 direction several hundred kilobases downstream of genes. The YFFF mutant shows reduced Pol II at promoterproximal 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.
机译:RNA聚合酶(POL)II的羧基 - 末端结构域(CTD)由Ysptsps庚段的重复组成,并用作调节RNA的转录,剪接和成熟的蛋白质复合物的装载平台。 在这里,我们研究了哺乳动物CTD突变体以分析转录循环中酪氨酸1残基的功能。 酪氨酸残基(YFFF突变体)的3/4的突变导致促进剂的反义方向的巨大读数转录表型以及在基因下游的30千碱基上的30个方向。 YFFF突变体显示出在促进剂促六泊暂停位点下的减少的POL II,丧失与介体和集成剂配合物的相互作用,并对这些络合物募集到染色质中受损。 与这些观察结果一致,在增强剂和SnRNA的成熟时加载POL II在基因组范围内改变。 我们得出结论,通过POL II的CTD控制终止的酪氨酸1残基。

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  • 来源
    《Molecular cell》 |2018年第1期|共20页
  • 作者单位

    Helmholtz Ctr Munich Dept Mol Epigenet Marchioninistr 25 D-81377 Munich Germany;

    Univ Montpellier CNRS IGMM Montpellier France;

    Univ Montpellier CNRS IGMM Montpellier France;

    Univ Montpellier CNRS IGMM Montpellier France;

    Univ Montpellier CNRS IGMM Montpellier France;

    ZFP Biomed Ctr Munich Grosshaderner Str 9 D-82152 Planegg Martinsried Germany;

    Helmholtz Ctr Munich Dept Mol Epigenet Marchioninistr 25 D-81377 Munich Germany;

    Univ Montpellier CNRS IGMM Montpellier France;

    Helmholtz Ctr Munich Dept Mol Epigenet Marchioninistr 25 D-81377 Munich Germany;

    Ludwig Maximilians Univ Munchen Gene Ctr Lab Funct Genome Anal Munich Germany;

    Ludwig Maximilians Univ Munchen Gene Ctr Lab Funct Genome Anal Munich Germany;

    ZFP Biomed Ctr Munich Grosshaderner Str 9 D-82152 Planegg Martinsried Germany;

    Helmholtz Ctr Munich Dept Mol Epigenet Marchioninistr 25 D-81377 Munich Germany;

    Univ Montpellier CNRS IGMM Montpellier France;

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  • 正文语种 eng
  • 中图分类 细胞生物学;
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