Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science. 2011 Jul 29;333(6042):633-7. doi: 10.1126/science.1206629.
The initiation of transcription by RNA polymerase II is a multistage process. X-ray crystal structures of transcription complexes containing short RNAs reveal three structural states: one with 2- and 3-nucleotide RNAs, in which only the 3'-end of the RNA is detectable; a second state with 4- and 5-nucleotide RNAs, with an RNA-DNA hybrid in a grossly distorted conformation; and a third state with RNAs of 6 nucleotides and longer, essentially the same as a stable elongating complex. The transition from the first to the second state correlates with a markedly reduced frequency of abortive initiation. The transition from the second to the third state correlates with partial "bubble collapse" and promoter escape. Polymerase structure is permissive for abortive initiation, thereby setting a lower limit on polymerase-promoter complex lifetime and allowing the dissociation of nonspecific complexes. Abortive initiation may be viewed as promoter proofreading, and the structural transitions as checkpoints for promoter control.
RNA 聚合酶 II 转录的起始是一个多步骤的过程。包含短 RNA 的转录复合物的 X 射线晶体结构揭示了三种结构状态：一种是具有 2 个和 3 个核苷酸的 RNA，其中仅能检测到 RNA 的 3'末端；第二种状态是具有 4 个和 5 个核苷酸的 RNA，具有严重扭曲构象的 RNA-DNA 杂交体；第三种状态是具有 6 个核苷酸及更长的 RNA，基本上与稳定的延伸复合物相同。从第一个状态到第二个状态的转变与明显降低的起始失败频率相关联。从第二个状态到第三个状态的转变与部分“泡崩溃”和启动子逃逸相关联。聚合酶结构允许起始失败，从而对聚合酶-启动子复合物的寿命设定下限，并允许非特异性复合物的解离。起始失败可能被视为启动子校对，而结构转变则是启动子控制的检查点。
