The Eightfold Path to non-enzymatic RNA replication

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The principal question in studies of abiogenesis centres on how the RNA World emerged from the prebiotic chemistry of the early Earth. Traditional models are based on the concept of an RNA replicase, but in the latest Perspective to be published in Journal of Systems Chemistry, Jack Szostak discusses the growing evidence that this process may have been chemically, rather than enzymatically driven.

The RNA World hypothesis proposes that current DNA-based life was predated by life based on RNA. While considerable evidence exists to support this model, there is still a lack of understanding regarding how cycles of template-directed RNA replication could occur. The original RNA World model was based around RNA-mediated catalysis but experimental demonstrations of RNA-catalyzed RNA copying have revealed significant barriers that would need to be overcome for this to be achieved.

“In light of [these] problems, I suggest that it is worthwhile to revisit the much earlier model of chemical (i.e., non-enzymatic) RNA replication”, explains Szostak, who identifies 8 issues that must be overcome in an experimental demonstration of RNA replication. While these perceived difficulties may make chemically-driven RNA replication seem even more challenging than the enzymatic process, Szostak’s Perspective addresses each one in turn, presenting recent evidence that shows there are potential solutions to all of these problems.

“Although a great deal of experimental work must yet be done, all of the major apparent stumbling blocks on the path to RNA replication appear to be at least potentially amenable to fairly simple solutions”.