Department of Biochemistry and Molecular Biology, The University of Chicago, Gordon Center for Integrative Science, Room W406, Chicago, IL 60637, USA.
Philos Trans R Soc Lond B Biol Sci. 2011 Oct 27;366(1580):2918-28. doi: 10.1098/rstb.2011.0144.
All models of the RNA world era invoke the presence of ribozymes that can catalyse RNA polymerization. The class I ligase ribozyme selected in vitro 15 years ago from a pool of random RNA sequences catalyses formation of a 3',5'-phosphodiester linkage analogous to a single step of RNA polymerization. Recently, the three-dimensional structure of the ligase was solved in complex with U1A RNA-binding protein and independently in complex with an antibody fragment. The RNA adopts a tripod arrangement and appears to use a two-metal ion mechanism similar to protein polymerases. Here, we discuss structural implications for engineering a true polymerase ribozyme and describe the use of the antibody framework both as a portable chaperone for crystallization of other RNAs and as a platform for exploring steps in evolution from the RNA world to the RNA-protein world.
RNA 世界时代的所有模型都假设存在能够催化 RNA 聚合的核酶。15 年前，从随机 RNA 序列库中体外选择的 I 类连接酶核酶催化形成 3'，5'-磷酸二酯键，类似于 RNA 聚合的单个步骤。最近，该连接酶的三维结构与 U1A RNA 结合蛋白复合物以及独立的抗体片段复合物已被解析。该 RNA 采用三脚排列，似乎使用类似于蛋白聚合酶的双金属离子机制。在这里，我们讨论了对工程化真正的聚合酶核酶的结构影响，并描述了抗体骨架的用途，既可以作为其他 RNA 结晶的可移动伴侣，也可以作为探索从 RNA 世界到 RNA-蛋白世界的进化步骤的平台。
