Tjhung, Katrina, Shokhirev, Maxim N., Horning, David P. and Joyce, Gerald F. (2020) An RNA polymerase ribozyme that synthesizes its own ancestor. Proceedings of the National Academy of Sciences. ISSN 0027-84241091-6490

Abstract

The RNA-based organisms from which modern life is thought to have descended would have depended on an RNA polymerase ribozyme to copy functional RNA molecules, including copying the polymerase itself. Such a polymerase must have been capable of copying structured RNAs with high efficiency and high fidelity to maintain genetic information across successive generations. Here the class I RNA polymerase ribozyme was evolved in vitro for the ability to synthesize functional ribozymes, resulting in the markedly improved ability to synthesize complex RNAs using nucleoside 5'-triphosphate (NTP) substrates. The polymerase is descended from the class I ligase, which contains the same catalytic core as the polymerase. The class I ligase can be synthesized by the improved polymerase as three separate RNA strands that assemble to form a functional ligase. The polymerase also can synthesize the complement of each of these three strands. Despite this remarkable level of activity, only a very small fraction of the assembled ligases retain catalytic activity due to the presence of disabling mutations. Thus, the fidelity of RNA polymerization should be considered a major impediment to the construction of a self-sustained, RNA-based evolving system. The propagation of heritable information requires both efficient and accurate synthesis of genetic molecules, a requirement relevant to both laboratory systems and the early history of life on Earth.

Item Type:	Article
Keywords:	directed evolution RNA enzyme RNA replication
Date Deposited:	15 Feb 2020 00:45
Last Modified:	15 Feb 2020 00:45
URI:	https://oak.novartis.com/id/eprint/40711