转录终止的反调节由哺乳动物的昼夜时钟 PERIOD 复合体
Kiran Padmanabhan1, Maria S Robles, Thomas Westerling
1Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
概括
哺乳动物的昼夜钟使用PERIOD (PER) 和CRYPTOCHROME (CRY) 复合体来抑制转录. 这些PER复合体直接控制转录终结,抑制RNA聚合酶II释放和重新启动.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 基因规则 基因规则
背景情况:
- 细胞的昼夜钟依赖于转录反循环进行调节.
- 在哺乳动物中,PERIOD (PER) 和CRYPTOCHROME (CRY) 蛋白质形成一个核复合体来抑制基因转录.
研究的目的:
- 研究PER复合体抑制转录的机制.
- 确定RNA螺旋酶和转录终结在昼夜负反中的作用.
主要方法:
- 分析小鼠PER复合物的组成.
- 在Per和Cry基因终结部位研究RNA聚合酶II的行为.
- 研究PER复合体与SETX之间的相互作用.
主要成果:
- 鼠标的PER复合体含有RNA基酶 (DDX5,DHX9),RNA聚合酶II和前mRNAs.
- 在昼夜负反过程中,RNA聚合酶II在Per和Cry基因的终结点积聚.
- PER复合体的招募抑制了转录终结因子SETX,阻碍了聚合酶的释放.
结论:
- 循环负反涉及对转录终止的直接调节.
- PER复合物通过抑制RNA聚合酶II在终结点的释放来积极抑制转录.
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