Rolling circle RNA synthesis catalyzed by RNA.
eLife Sciences Publications, Ltd
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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
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.
Research Article, Biochemistry and Chemical Biology, origin of life, rolling circle, circular RNA, ribozymes, None
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)
External DOI: https://doi.org/10.7554/eLife.75186
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335281