SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination
SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination
复制标题
DOI：
10.1038/nature16469
复制
发表时间：
2016-01-07
期刊：
影响因子：
64.8
通讯作者：
Greenblatt, Jack F.
中科院分区：
文献类型：
--
作者：
Zhao, Dorothy Yanling;Gish, Gerald;Greenblatt, Jack F.
RNA聚合酶II（RNAP II）亚基POLR 2A的羧基末端结构域（CTD）是一个修饰平台，用于指定调节转录、mRNA加工和染色质重塑的因子的募集。在这里，我们表明，CTD精氨酸残基（R1810在人类）是保守的脊椎动物是对称二甲基化（me 2s）。这种R1810 me 2s修饰需要蛋白质精氨酸甲基转移酶5（PRMT 5）并募集运动神经元存活（SMN，也称为GEMIN 1）蛋白的Tudor结构域，其在脊髓性肌萎缩症中突变。SMN与senataxin相互作用，senataxin有时在共济失调性眼用不能2型和肌萎缩侧索硬化症中突变。由于POLR 2A R1810 me 2s和SMN，像senataxin一样，需要解决RNA聚合酶II在转录终止区形成R环的RNA-DNA杂交体，我们建议R1810 me 2s，SMN和senataxin是R环解析途径的组成部分。该途径的缺陷可影响转录终止，并可能导致神经退行性疾病。
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.