Genomics and Cell Biology

A Model For The Emergence of RNA From A Prebiotically Plausible Mixture of Ribonucleotides, Arabinonucleotides and 2'-deoxynucleotides

By Keith Cowing
Press Release
November 28, 2019
Filed under
A Model For The Emergence of RNA From A Prebiotically Plausible Mixture of Ribonucleotides, Arabinonucleotides and 2'-deoxynucleotides
Crystal structure of RNA primer/template complex with an arabinonucleotide at the 3′-end of the primer (PDB 6OWL). Red: primer; green: GMP monomers. The wheat mesh indicates the 2Fo − Fc omit map contoured at 1.5σ. (A) Schematic of the primer/template complex. Italic letters: locked nucleotides; aG at the 3′ end: arabino-guanosine. (B) Overall structure of the 3′-arabino RNA-GMP complex, stacking with neighboring complexes. (C) The local structure of the arabino-G-terminated primer. The corresponding omit map indicates that the primer arabinose is in the C2′-endo conformation, and the guanine is Watson-Crick base paired with the template. (D) The GMP monomers are bound through both canonical and non-canonical G:C base pairs. The primer 2′-OH and N7 of the +1 GMP monomer are within hydrogen bonding distance.

The abiotic synthesis of ribonucleotides is thought to have been an essential step towards the emergence of the RNA world.

However, it is likely that the prebiotic synthesis of ribonucleotides was accompanied by the simultaneous synthesis of arabinonucleotides, 2′-deoxyribonucleotides, and other variations on the canonical nucleotides. In order to understand how relatively homogeneous RNA could have emerged from such complex mixtures, we have examined the properties of arabinonucleotides and 2′-deoxyribonucleotides in nonenzymatic template-directed primer extension reactions.

We show that nonenzymatic primer extension with activated arabinonucleotides is much less efficient than with activated ribonucleotides, and furthermore that once an arabinonucleotide is incorporated, continued primer extension is strongly inhibited. As previously shown, 2′-deoxyribonucleotides are also less efficiently incorporated in primer extension reactions, but the difference is more modest. Experiments with mixtures of nucleotides suggest that the coexistence of ribo- and arabino-nucleotides does not impede the copying of RNA templates. Moreover, chimeric oligoribonucleotides containing 2′-deoxy- or arabino-nucleotides are effective templates for RNA synthesis.

We propose that the initial genetic polymers were random sequence chimeric oligonucleotides formed by untemplated polymerization, but that template copying chemistry favored RNA synthesis; multiple rounds of replication may have led to pools of oligomers composed mainly of RNA.

Seohyun Chris Kim, Lijun Zhou, Wen Zhang, Derek K. O’Flaherty, Valeria Rondo-Brovetto, Jack W. Szostak
This article is a preprint and has not been certified by peer review

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