Molecular Basis of RNA Polymerase III Transcription Repression by Maf1
Molecular Basis of RNA Polymerase III Transcription Repression by Maf1
复制标题
DOI：
10.1016/j.cell.2010.09.002
复制
发表时间：
2010-10
期刊：
影响因子：
64.5
通讯作者：
A. Vannini;R. Ringel;A. Kusser;O. Berninghausen;G. Kassavetis;P. Cramer
中科院分区：
文献类型：
--
作者：
A. Vannini;R. Ringel;A. Kusser;O. Berninghausen;G. Kassavetis;P. Cramer
RNA聚合酶III（Pol III）转录细胞生长所需的短RNA。在胁迫条件下，保守蛋白Maf 1迅速抑制Pol III转录。我们报告Maf 1的晶体结构和Pol III，一个活跃的Pol III-DNA-RNA复合物和一个抑制性Pol III-Maf 1复合物的冷冻电子显微镜结构。DNA和RNA的结合导致转录起始所需的Pol III特异性亚复合物C82/34/31的排序。Maf 1结合Pol III钳并在活性中心裂缝的边缘重排C82/34/31。这损害了Pol III向启动子DNA与起始因子Brf 1和TBP的复合物的募集，从而防止闭合复合物的形成。然而，Maf 1不损害DNA-RNA支架的结合和RNA合成。这些结果解释了Maf 1如何特异性地抑制Pol III启动子的转录起始，并表明Maf 1还通过在转录延伸期间结合Pol III来防止再起始。
RNA polymerase III (Pol III) transcribes short RNAs required for cell growth. Under stress conditions, the conserved protein Maf1 rapidly represses Pol III transcription. We report the crystal structure of Maf1 and cryo-electron microscopic structures of Pol III, an active Pol III-DNA-RNA complex, and a repressive Pol III-Maf1 complex. Binding of DNA and RNA causes ordering of the Pol III-specific subcomplex C82/34/31 that is required for transcription initiation. Maf1 binds the Pol III clamp and rearranges C82/34/31 at the rim of the active center cleft. This impairs recruitment of Pol III to a complex of promoter DNA with the initiation factors Brf1 and TBP and thus prevents closed complex formation. Maf1 does however not impair binding of a DNA-RNA scaffold and RNA synthesis. These results explain how Maf1 specifically represses transcription initiation from Pol III promoters and indicate that Maf1 also prevents reinitiation by binding Pol III during transcription elongation.