Structural Basis of RNA Polymerase I Transcription Initiation
Structural Basis of RNA Polymerase I Transcription Initiation
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DOI：
10.1016/j.cell.2017.03.003
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发表时间：
2017-03-23
期刊：
影响因子：
64.5
通讯作者：
Cramer, Patrick
中科院分区：
文献类型：
--
作者：
Engel, Christoph;Gubbey, Tobias;Cramer, Patrick
在核糖体RNA启动子处的转录起始需要RNA聚合酶（Pol）I和起始因子Rrn 3和核心因子（CF）。在这里，我们结合联合收割机X射线晶体学和冷冻电子显微镜（cryo-EM），以获得一个分子模型的基础Pol I启动。三亚基CF结合上游启动子DNA，对接到Pol I-Rrn（3）复合物，并将DNA加载到聚合酶的扩展活性中心裂缝中。Pol I突起和钳结构域之间的DNA解旋使得裂缝收缩，导致活性Pol I构象和RNA合成。与Pol II系统的比较表明，启动子特异性依赖于启动子序列的独特“弯曲性”和“可熔性”，这使得启动因子、DNA和聚合酶之间能够接触。
Transcription initiation at the ribosomal RNA promoter requires RNA polymerase (Pol) I and the initiation factors Rrn3 and core factor (CF). Here, we combine X-ray crystallography and cryo-electron microscopy (cryo-EM) to obtain a molecular model for basal Pol I initiation. The three-subunit CF binds upstream promoter DNA, docks to the Pol I-Rrn(3) complex, and loads DNA into the expanded active center cleft of the polymerase. DNA unwinding between the Pol I protrusion and clamp domains enables cleft contraction, resulting in an active Pol I conformation and RNA synthesis. Comparison with the Pol II system suggests that promoter specificity relies on a distinct "bendability'' and "meltability'' of the promoter sequence that enables contacts between initiation factors, DNA, and polymerase.