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RNA-Catalyzed Cross-Chiral Polymerization of RNA

Tjhung, Katrina and Sczepanski, Jonathan and Murtfeldt, Eric and Joyce, Gerald (2020) RNA-Catalyzed Cross-Chiral Polymerization of RNA. Journal of the American Chemical Society JACS., 142 (36). pp. 15331-15339. ISSN 0002-78631520-5126

Abstract

Biology relies almost exclusively on homochiral building blocks to drive the processes
of life. Yet cross-chiral interactions can occur between macromolecules of the opposite
handedness, including a previously described polymerase ribozyme that catalyzes the template-directed synthesis of enantio-RNA. The present study sought to optimize and generalize this
activity, employing in vitro evolution to select cross-chiral polymerases that use either mono- or
trinucleotide substrates that are activated as the 5´-triphosphate. There was only modest
improvement of the former activity, but dramatic improvement of the latter, which enables the
trinucleotide polymerase to react 10^2–10^3-fold faster than its ancestor and to accept substrates
with all possible sequence combinations. The evolved ribozyme can assemble long RNAs from a
mixture of trinucleotide building blocks, including a two-fragment form of the ancestral
polymerase ribozyme. Further improvement of this activity could enable the generalized cross-chiral
replication of RNA, which would establish a new paradigm for the chemical basis of
Darwinian evolution.

Item Type: Article
Date Deposited: 29 Sep 2020 00:45
Last Modified: 29 Sep 2020 00:45
URI: https://oak.novartis.com/id/eprint/42691

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