Ribozyme-catalysed RNA synthesis using triplet building blocks
RNA-catalyzed RNA replication is widely believed to have supported a primordial biology. However, RNA catalysis is dependent upon RNA folding, and this yields structures that can block replication of such RNAs. To address this apparent paradox we have re-examined the building blocks used for RNA replication. We report RNA-catalysed RNA synthesis on structured templates when using trinucleotide triphosphates (triplets) as substrates, catalysed by a general and accurate triplet polymerase ribozyme that emerged from in vitro evolution as a mutualistic RNA heterodimer. The triplets cooperatively invaded and unraveled even highly stable RNA secondary structures, and support non-canonical primer-free and bidirectional modes of RNA synthesis and replication. Triplet substrates thus resolve a central incongruity of RNA replication, and here allow the ribozyme to synthesise its own catalytic subunit '+' and '-' strands in segments and assemble them into a new active ribozyme.
All data generated during this study and collated sequencing results are included in the manuscript and its supporting files. Source data files have been provided for Figures 1-4, 8 and 9.
Article and author information
Medical Research Council (MC_U105178804)
- Philipp Holliger
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Anna Marie Pyle, Yale University, United States
- Received: January 19, 2018
- Accepted: May 9, 2018
- Accepted Manuscript published: May 15, 2018 (version 1)
- Version of Record published: June 15, 2018 (version 2)
© 2018, Attwater et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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