Regensburg Center for Biochemistry, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
Nat Commun. 2021 Feb 3;12(1):758. doi: 10.1038/s41467-021-21031-8.
RNA polymerase (Pol) I transcribes the ribosomal RNA precursor in all eukaryotes. The mechanisms 'activation by cleft contraction' and 'hibernation by dimerization' are unique to the regulation of this enzyme, but structure-function analysis is limited to baker's yeast. To understand whether regulation by such strategies is specific to this model organism or conserved among species, we solve three cryo-EM structures of Pol I from Schizosaccharomyces pombe in different functional states. Comparative analysis of structural models derived from high-resolution reconstructions shows that activation is accomplished by a conserved contraction of the active center cleft. In contrast to current beliefs, we find that dimerization of the S. pombe polymerase is also possible. This dimerization is achieved independent of the 'connector' domain but relies on two previously undescribed interfaces. Our analyses highlight the divergent nature of Pol I transcription systems from their counterparts and suggest conservation of regulatory mechanisms among organisms.
RNA 聚合酶（Pol）I 在所有真核生物中转录核糖体 RNA 前体。“裂隙收缩激活”和“二聚体化休眠”的机制是该酶调控所特有的，但结构-功能分析仅限于面包酵母。为了了解这种策略的调控是否仅针对该模式生物或在物种间保守，我们解析了三种不同功能状态的裂殖酵母 Pol I 的冷冻电镜结构。来自高分辨率重构的结构模型的比较分析表明，激活是通过活性中心裂隙的保守收缩来实现的。与当前的观点相反，我们发现聚酶 I 的二聚化也是可能的。这种二聚化的实现不依赖于“连接”结构域，但依赖于两个以前未描述的界面。我们的分析强调了 Pol I 转录系统与其对应物的不同性质，并表明调控机制在生物间是保守的。
