TY - JOUR TI - Rolling circle RNA synthesis catalyzed by RNA AU - Kristoffersen, Emil Laust AU - Burman, Matthew AU - Noy, Agnes AU - Holliger, Philipp A2 - Nilsen, Timothy W A2 - Manley, James L A2 - Sponer, Jiri VL - 11 PY - 2022 DA - 2022/02/02 SP - e75186 C1 - eLife 2022;11:e75186 DO - 10.7554/eLife.75186 UR - https://doi.org/10.7554/eLife.75186 AB - 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. KW - origin of life KW - rolling circle KW - circular RNA KW - ribozymes JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -