Non-enzymatic primer extension with strand displacement
- Howard Hughes Medical Institute, Massachusetts General Hospital, United States
- Harvard University, United States
Abstract
Non-enzymatic RNA self-replication is integral to the emergence of the 'RNA World'. Despite considerable progress in non-enzymatic template copying, demonstrating a full replication cycle remains challenging due to the difficulty of separating the strands of the product duplex. Here, we report a prebiotically plausible approach to strand displacement synthesis in which short 'invader' oligonucleotides unwind an RNA duplex through a toehold/branch migration mechanism, allowing non-enzymatic primer extension on a template that was previously occupied by its complementary strand. Kinetic studies of single-step reactions suggest that following invader binding, branch migration results in a 2:3 partition of the template between open and closed states. Finally, we demonstrate continued primer extension with strand displacement by employing activated 3′-aminonucleotides, a more reactive proxy for ribonucleotides. Our study suggests that complete cycles of non-enzymatic replication of the primordial genetic material may have been facilitated by short RNA oligonucleotides.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
Simons Foundation (290363)
- Jack W Szostak
National Science Foundation (CHE-1607034)
- Jack W Szostak
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Zhou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Non-enzymatic primer extension with strand displacement
eLife 8:e51888.
https://doi.org/10.7554/eLife.51888
