Kristoffersen, Emil Laust, Burman, Matthew, Noy, Agnes orcid.org/0000-0003-0673-8949 et al. (1 more author) (2022) Rolling circle RNA synthesis catalysed by RNA. eLife. e75186. ISSN 2050-084X
Abstract
RNA-catalysed RNA replication is widely considered a key step in the emergence of life's first genetic system. However, RNA replication can be impeded by the extraordinary stability of duplex RNA products, which must be dissociated for re-initiation of the next replication cycle. Here we have explored rolling circle synthesis (RCS) as a potential solution to this strand separation problem. We observe sustained RCS by a triplet polymerase ribozyme beyond full-length circle synthesis with strand displacement yielding concatemeric RNA products. Furthermore, we show RCS of a circular Hammerhead ribozyme capable of self-cleavage and re-circularisation. Thus, all steps of a viroid-like RNA replication pathway can be catalysed by RNA alone. Finally, we explore potential RCS mechanisms by molecular dynamics simulations, which indicate a progressive build-up of conformational strain upon RCS' with destabilisation of nascent strand 5'- and 3'-ends. Our results have implications for the emergence of RNA replication and for understanding the potential of RNA to support complex genetic processes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022, Kristoffersen et al. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Physics (York) |
Funding Information: | Funder Grant number EPSRC EP/V520561/1 EPSRC EP/N027639/1 |
Depositing User: | Pure (York) |
Date Deposited: | 12 May 2022 11:30 |
Last Modified: | 22 Jan 2025 00:18 |
Published Version: | https://doi.org/10.7554/eLife.75186 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.7554/eLife.75186 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:186773 |
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Filename: elife_75186_v3.pdf
Description: Rolling circle RNA synthesis catalyzed by RNA
Licence: CC-BY 2.5