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SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination

机译:SMN和对称精氨酸二甲基化的RNA聚合酶II C末端域控制终止

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摘要

The carboxy-terminal domain (CTD) of the RNA polymerase II (RNAP II) subunit POLR2A is a platform for modifications specifying the recruitment of factors that regulate transcription, mRNA processing, and chromatin remodelling. Here we show that a CTD arginine residue (R1810 in human) that is conserved across vertebrates is symmetrically dimethylated (me2s). This R1810me2s modification requires protein arginine methyltransferase 5 (PRMT5) and recruits the Tudor domain of the survival of motor neuron (SMN, also known as GEMIN1) protein, which is mutated in spinal muscular atrophy. SMN interacts with senataxin, which is sometimes mutated in ataxia oculomotor apraxia type 2 and amyotrophic lateral sclerosis. Because POLR2A R1810me2s and SMN, like senataxin, are required for resolving RNA-DNA hybrids created by RNA polymerase II that form R-loops in transcription termination regions, we propose that R1810me2s, SMN, and senataxin are components of an R-loop resolution pathway. Defects in this pathway can influence transcription termination and may contribute to neurodegenerative disorders.
机译:RNA聚合酶II(RNAP II)亚基POLR2A的羧基末端结构域(CTD)是修饰平台,用于指定募集调节转录,mRNA加工和染色质重塑的因子。在这里,我们显示了在整个脊椎动物中保守的CTD精氨酸残基(在人类中为R1810)是对称的二甲基化(me2s)。这种R1810me2s修饰需要蛋白质精氨酸甲基转移酶5(PRMT5),并募集运动神经元(SMN,也称为GEMIN1)蛋白质存活的Tudor域,该蛋白质在脊髓性肌萎缩症中发生突变。 SMN与senataxin相互作用,而senataxin有时在共济失调动眼性运动失用2型和肌萎缩性侧索硬化症中发生突变。由于POLR2A R1810me2s和SMN像senataxin一样,是解决由RNA聚合酶II创建的在转录终止区域形成R环的RNA-DNA杂种所必需的,因此我们建议R1810me2s,SMN和senataxin是R环分解途径的组成部分。该途径中的缺陷可能影响转录终止,并可能导致神经退行性疾病。

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  • 来源
    《Nature》 |2016年第7584期|48-53|共6页
  • 作者单位

    Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada|Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada|Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada;

    Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada;

    Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada;

    Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada|Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3G4, Canada;

    Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada;

    Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada;

    Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada;

    Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada;

    Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada;

    Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada|Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada;

    Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada;

    Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada;

    Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada|Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada;

    Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada|Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada;

    Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada|Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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