MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
Nat Chem. 2013 Dec;5(12):1011-8. doi: 10.1038/nchem.1781. Epub 2013 Oct 20.
Mechanisms of molecular self-replication have the potential to shed light on the origins of life. In particular, self-replication through RNA-catalysed templated RNA synthesis is thought to have supported a primordial 'RNA world'. However, existing polymerase ribozymes lack the capacity to synthesize RNAs approaching their own size. Here, we report the in vitro evolution of such catalysts directly in the RNA-stabilizing medium of water ice, which yielded RNA polymerase ribozymes specifically adapted to sub-zero temperatures and able to synthesize RNA in ices at temperatures as low as -19 °C. The combination of cold-adaptive mutations with a previously described 5' extension operating at ambient temperatures enabled the design of a first polymerase ribozyme capable of catalysing the accurate synthesis of an RNA sequence longer than itself (adding up to 206 nucleotides), an important stepping stone towards RNA self-replication.
分子自我复制的机制有可能为生命起源提供线索。特别是，通过 RNA 催化的模板 RNA 合成的自我复制被认为支持了原始的“RNA 世界”。然而，现有的聚合酶核酶缺乏合成接近自身大小的 RNA 的能力。在这里，我们报告了在水冰的 RNA 稳定介质中直接进行的此类催化剂的体外进化，这产生了专门适应低温的 RNA 聚合酶核酶，能够在低至-19°C 的冰中合成 RNA。将低温适应突变与之前描述的在环境温度下工作的 5' 延伸相结合，使设计出第一个能够催化自身长度以上的 RNA 序列（最多添加 206 个核苷酸）的精确合成的聚合酶核酶成为可能，这是 RNA 自我复制的重要一步。
