RNA polymerase I structure and transcription regulation

RNA polymerase I structure and transcription regulation
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DOI:
10.1038/nature12712
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发表时间:
2013-10-31
期刊:
影响因子:
64.8
通讯作者:
Cramer, Patrick
Cramer, Patrick
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Engel, Christoph;Sainsbury, Sarah;Cramer, Patrick

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RNA聚合酶(Pol)I转录核糖体RNA,启动核糖体的生物合成,调节真核细胞的生长。酿酒酵母Pol I的晶体结构在2.8埃分辨率下显示了590千道尔顿酶的全部14个亚基,并显示了与Pol II的不同。一个‘扩张器’元件占据了DNA模板位置,并通过一个展开的桥式螺旋稳定了一个扩展的活性中心裂隙。“连接器”元件侵入邻近聚合酶的裂隙,并稳定不活跃的聚合酶二聚体。在Pol I激活过程中,连接器和扩张器必须分离,才能通过聚合酶“核心”和“架子”模块的会聚运动来启动转录和裂解收缩。非活性的扩展聚合酶状态和活性的收缩聚合酶状态之间的转换通常可能是转录的基础。调节因子可以调节核心-搁板界面,该界面包括RNA链的起始、延伸、校对和终止的“复合”活性部位。
Transcription of ribosomal RNA by RNA polymerase (Pol) I initiates ribosome biogenesis and regulates eukaryotic cell growth. The crystal structure of Pol I from the yeast Saccharomyces cerevisiae at 2.8 angstrom resolution reveals all 14 subunits of the 590-kilodalton enzyme, and shows differences to Pol II. An 'expander' element occupies the DNA template site and stabilizes an expanded active centre cleft with an unwound bridge helix. A 'connector' element invades the cleft of an adjacent polymerase and stabilizes an inactive polymerase dimer. The connector and expander must detach during Pol I activation to enable transcription initiation and cleft contraction by convergent movement of the polymerase 'core' and 'shelf' modules. Conversion between an inactive expanded and an active contracted polymerase state may generally underlie transcription. Regulatory factors can modulate the core-shelf interface that includes a 'composite' active site for RNA chain initiation, elongation, proofreading and termination.