Rolling circle RNA synthesis catalyzed by RNA
RNA-catalyzed 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 explo...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/75186 |
| _version_ | 1797991970002436096 |
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| author | Emil Laust Kristoffersen Matthew Burman Agnes Noy Philipp Holliger |
| author_facet | Emil Laust Kristoffersen Matthew Burman Agnes Noy Philipp Holliger |
| author_sort | Emil Laust Kristoffersen |
| collection | DOAJ |
| description | RNA-catalyzed 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-circularization. Thus, all steps of a viroid-like RNA replication pathway can be catalyzed 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 destabilization 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. |
| first_indexed | 2024-04-11T08:59:28Z |
| format | Article |
| id | doaj.art-6bb094d8d2d9494f9c7eb9faf7699a8d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T08:59:28Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6bb094d8d2d9494f9c7eb9faf7699a8d2022-12-22T04:32:49ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.75186Rolling circle RNA synthesis catalyzed by RNAEmil Laust Kristoffersen0https://orcid.org/0000-0001-8965-8201Matthew Burman1Agnes Noy2https://orcid.org/0000-0003-0673-8949Philipp Holliger3https://orcid.org/0000-0002-3440-9854MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United KingdomDepartment of Physics, University of York, York, United KingdomDepartment of Physics, University of York, York, United KingdomMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, United KingdomRNA-catalyzed 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-circularization. Thus, all steps of a viroid-like RNA replication pathway can be catalyzed 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 destabilization 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.https://elifesciences.org/articles/75186origin of liferolling circlecircular RNAribozymes |
| spellingShingle | Emil Laust Kristoffersen Matthew Burman Agnes Noy Philipp Holliger Rolling circle RNA synthesis catalyzed by RNA eLife origin of life rolling circle circular RNA ribozymes |
| title | Rolling circle RNA synthesis catalyzed by RNA |
| title_full | Rolling circle RNA synthesis catalyzed by RNA |
| title_fullStr | Rolling circle RNA synthesis catalyzed by RNA |
| title_full_unstemmed | Rolling circle RNA synthesis catalyzed by RNA |
| title_short | Rolling circle RNA synthesis catalyzed by RNA |
| title_sort | rolling circle rna synthesis catalyzed by rna |
| topic | origin of life rolling circle circular RNA ribozymes |
| url | https://elifesciences.org/articles/75186 |
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