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在 RNA 世界中进行连续的 RNA 聚合和启动子识别。

Processive RNA polymerization and promoter recognition in an RNA World.

机构信息

Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.

出版信息

Science. 2021 Mar 19;371(6535):1225-1232. doi: 10.1126/science.abd9191.

Abstract

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.

摘要

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。

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