Rolling circle RNA synthesis catalyzed by RNA.
Publication Date
2022-02-02Journal Title
Elife
ISSN
2050-084X
Publisher
eLife Sciences Publications, Ltd
Volume
11
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Kristoffersen, E. L., Burman, M., Noy, A., & Holliger, P. (2022). Rolling circle RNA synthesis catalyzed by RNA.. Elife, 11 https://doi.org/10.7554/eLife.75186
Abstract
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.
Keywords
Research Article, Biochemistry and Chemical Biology, origin of life, rolling circle, circular RNA, ribozymes, None
Sponsorship
Carlsbergfondet (CF17-0809 & CF19-0019)
Medical Research Council (MC_U105178804)
Engineering and Physical Sciences Research Council (EP/N027639/1)
Engineering and Physical Sciences Research Council (EP/R513386/1)
Engineering and Physical Sciences Research Council (EP/T022205/1)
Identifiers
75186
External DOI: https://doi.org/10.7554/eLife.75186
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335281
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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