Wachowius Falk, Holliger Philipp
Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH (UK).
ChemSystemsChem. 2019 Jul;1(1-2):1-4. doi: 10.1002/syst.201900004. Epub 2019 Feb 20.
Central to the "RNA world" hypothesis of the origin of life is the emergence of an RNA catalyst capable of RNA replication. However, possible replicase ribozymes are quite complex and were likely predated by simpler non-enzymatic replication reactions. The templated polymerisation of phosphorimidazolide (Imp) activated ribonucleotides currently appears as the most tractable route to both generate and replicate short RNA oligomer pools from which a replicase could emerge. Herein we demonstrate the rapid assembly of complex ribozymes from such Imp-activated RNA fragment pools. Specifically, we show assembly of a newly selected minimal RNA polymerase ribozyme variant (150 nt) by RNA templated ligation of 5'-2-methylimidazole-activated RNA oligomers <30 nucleotides long. Our results provide support for the possibility that complex RNA structures could have emerged from pools of activated RNA oligomers and outlines a path for the transition from non-enzymatic/chemical to enzymatic RNA replication.
生命起源的“RNA世界”假说的核心是出现一种能够进行RNA复制的RNA催化剂。然而，可能的复制酶核酶相当复杂，并且很可能在更简单的非酶促复制反应之前就已存在。目前，磷酰咪唑（Imp）活化的核糖核苷酸的模板聚合似乎是从短RNA寡聚物库中生成并复制出复制酶的最可行途径。在此，我们展示了从这种Imp活化的RNA片段库中快速组装复杂核酶的过程。具体而言，我们通过RNA模板连接长度小于30个核苷酸的5'-2-甲基咪唑活化的RNA寡聚物，展示了一种新选择的最小RNA聚合酶核酶变体（150个核苷酸）的组装。我们的结果为从活化RNA寡聚物库中出现复杂RNA结构的可能性提供了支持，并概述了从非酶促/化学复制到酶促RNA复制的转变路径。
