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Rolling circle RNA synthesis catalyzed by RNA.

Published version
Peer-reviewed

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Authors

Kristoffersen, Emil Laust  ORCID logo  https://orcid.org/0000-0001-8965-8201
Burman, Matthew 

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.

Description

Keywords

biochemistry, chemical biology, circular RNA, none, origin of life, ribozymes, rolling circle, Catalysis, RNA, RNA, Viral, Recombination, Genetic, Viroids, Virus Replication

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

11

Publisher

eLife Sciences Publications, Ltd

Rights

Attribution 4.0 International
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)