Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, 16802, PA, USA.
Department of Medicine, Pennsylvania State University, Hershey, 17033, PA, USA.
Nat Commun. 2020 Jul 10;11(1):3474. doi: 10.1038/s41467-020-17308-z.
RNase MRP is an essential eukaryotic ribonucleoprotein complex involved in the maturation of rRNA and the regulation of the cell cycle. RNase MRP is related to the ribozyme-based RNase P, but it has evolved to have distinct cellular roles. We report a cryo-EM structure of the S. cerevisiae RNase MRP holoenzyme solved to 3.0 Å. We describe the structure of this 450 kDa complex, interactions between its components, and the organization of its catalytic RNA. We show that some of the RNase MRP proteins shared with RNase P undergo an unexpected RNA-driven remodeling that allows them to bind to divergent RNAs. Further, we reveal how this RNA-driven protein remodeling, acting together with the introduction of new auxiliary elements, results in the functional diversification of RNase MRP and its progenitor, RNase P, and demonstrate structural underpinnings of the acquisition of new functions by catalytic RNPs.
核糖核酸酶 MRP 是一种必需的真核核糖核蛋白复合物，参与 rRNA 的成熟和细胞周期的调控。核糖核酸酶 MRP 与基于核酶的核糖核酸酶 P 相关，但它已经进化出了不同的细胞功能。我们报道了酿酒酵母核糖核酸酶 MRP 全酶的冷冻电镜结构，分辨率为 3.0Å。我们描述了这个 450kDa 复合物的结构、其组件之间的相互作用以及其催化 RNA 的组织方式。我们表明，与核糖核酸酶 P 共享的一些核糖核酸酶 MRP 蛋白经历了一种意想不到的 RNA 驱动的重塑，使它们能够结合到不同的 RNA 上。此外，我们揭示了这种 RNA 驱动的蛋白质重塑，与引入新的辅助元件一起，导致核糖核酸酶 MRP 和其前体核糖核酸酶 P 的功能多样化，并展示了催化 RNA 获得新功能的结构基础。
