Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
Science. 2021 Mar 19;371(6535):1225-1232. doi: 10.1126/science.abd9191.
Early life is thought to have required the self-replication of RNA by RNA replicases. However, how such replicases evolved and subsequently enabled gene expression remains largely unexplored. We engineered and selected a holopolymerase ribozyme that uses a sigma factor-like specificity primer to first recognize an RNA promoter sequence and then, in a second step, rearrange to a processive elongation form. Using its own sequence, the polymerase can also program itself to polymerize from certain RNA promoters and not others. This selective promoter-based polymerization could allow an RNA replicase ribozyme to define "self" from "nonself," an important development for the avoidance of replicative parasites. Moreover, the clamp-like mechanism of this polymerase could eventually enable strand invasion, a critical requirement for replication in the early evolution of life.
早期生命被认为需要 RNA 复制酶通过 RNA 进行自我复制。然而,这种复制酶是如何进化的,以及随后如何使基因表达成为可能,在很大程度上仍未得到探索。我们设计并选择了一种全聚合酶核酶,它使用类似于σ因子的特异性引物首先识别 RNA 启动子序列,然后在第二步重新排列为连续延伸形式。聚合酶可以使用自身的序列将自身编程为从某些 RNA 启动子聚合,而不从其他启动子聚合。这种基于选择性启动子的聚合作用可以使 RNA 复制酶核酶从“非自我”中定义“自我”,这对于避免复制寄生虫是一个重要的发展。此外,这种聚合酶的夹状机制最终可能使链入侵成为可能,这是生命早期复制的一个关键要求。