通过酸化调节的RNA聚合酶II与低复杂度域的纤维聚合物结合
Ilmin Kwon1, Masato Kato1, Siheng Xiang1
1Department of Biochemistry University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75390-9152.
Cell
|November 26, 2013
概括
来自FUS,EWS和TAF15蛋白质的低复杂性域形成结合RNA聚合酶II的纤维. 这种结合通过CTD酸化是可逆的,这解释了转录期间的基因激活和释放.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 生物化学 生物化学
背景情况:
- FUS,EWS和TAF15基因的低复杂性 (LC) 域与DNA结合域融合时,与癌症形成有关.
- 在融合蛋白中,这些LC域充当转录激活域.
研究的目的:
- 调查FUS,EWS和TAF15的LC域招募RNA聚合酶II的机制.
- 阐明LC域聚合和RNA聚合酶II C终端域 (CTD) 酸化在转录调节中的作用.
主要方法:
- 试验室结合试验用于研究LC域聚合物与RNA聚合酶II的CTD之间的相互作用.
- 对LC域和CTD重复的突变分析以确定对结合亲和和转录激活的影响.
- 酸化试验用于评估CTD-LC域结合的可逆性.
主要成果:
- 由FUS,EWS和TAF15LC域形成的聚合纤维直接与RNA聚合酶II的CTD结合.
- 这种结合是可逆的,通过对CTD的代七度重复的酸化.
- 转录激活的强度与CTD和LC域聚合物之间的结合亲和关系.
结论:
- LC域聚合物作为RNA聚合酶II的非酸化CTD的直接结合接口,促进基因招募.
- CTD的七度重复的酸化释放RNA聚合酶II,允许转录延长.
- 这为了解活性基因中RNA聚合酶II的动态招募和释放提供了一个模型.
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