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Effect of 'spent'nucleotides' on nonenzymatic RNA replication

Patki, G. M.; Rajamani, S.

2023-07-21 biochemistry
10.1101/2023.07.20.549979 bioRxiv
Show abstract

Nonenzymatic template-directed replication would have been affected by co-solutes in a heterogenous prebiotic soup due to lack of enzymatic machinery. Unlike in contemporary biology, these reactions use chemically-activated nucleotides, which undergo rapid hydrolysis forming nucleoside monophosphates ( spent monomers). These co-solutes cannot extend the primer but continue to base pair with the template, thereby interfering with replication. We therefore aimed to understand how a mixture of spent ribonucleotides would affect nonenzymatic replication. We observed inhibition of replication in presence of the mixture, wherein predominant contribution came from the cognate Watson-Crick monomer, showing potential sequence dependence. Our study highlights how nonenzymatic RNA replication would have been directly affected by co-solutes, with ramifications for the emergence of functional polymers in an RNA World.

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