期刊
ELIFE
卷 11, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.75186
关键词
origin of life; rolling circle; circular RNA; ribozymes; None
类别
资金
- Carlsberg Foundation [CF17-0809]
- Medical Research Council (MRC) program Grant program [MC_U105178804]
- Engineering and Physical Sciences Research Council (EPSRC) [EP/N027639/1]
- EPSRC [EP/R513386/1, EP/T022205/1, EP/R029407/1, EP/P020259/1]
- MRC [MC_U105178804] Funding Source: UKRI
RNA-catalyzed RNA replication is a crucial step in the emergence of life's first genetic system. This study explores rolling circle synthesis as a potential solution to the problem of strand separation. The results demonstrate that RNA can catalyze all steps of viroid-like RNA replication, and molecular dynamics simulations provide insights into the potential mechanism of rolling circle synthesis.
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 & PRIME;- and 3 & PRIME;-ends. Our results have implications for the emergence of RNA replication and for understanding the potential of RNA to support complex genetic processes.
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