Functional interactions between proteins and nucleic acids are a hallmark of life on Earth. We hypothesize that cooperative interactions involving proteins and nucleic acids extended back to an era when early chemical evolution was shaped by synergistic interactions, or mutualism, between proto-peptides and proto-nucleic acids. It is likely that the polypeptide backbone is the product of chemical evolution, and is a descendant of ancestral proto-peptides composed of monomers that condense readily under prebiotic conditions. It is now known that depsipeptides, which contain mixtures of ester and amide linkages, can form spontaneously upon drying and heating of mixtures of hydroxy acids with amino acids.<br/>Here we show that cationic proto-peptides (depsipeptides and polyesters), either produced as mixtures from plausibly prebiotic dry-down reactions or synthetically prepared in pure form, can engage in direct, mutually-stabilizing interactions with RNA. Cationic proto-peptides significantly increased the thermal stability of folded RNA structures; we show that the addition of a depsipeptide can shift the extent of RNA duplex hybridization from &lt;10% to ~85% hybridized. In turn, RNA can reduce the rate of hydrolysis of depsipeptide ester bonds by &gt;30-fold. Proto-peptides containing proteinaceous amino acids adjacent to ester bonds generally promoted RNA duplex thermal stability to a greater magnitude than did analogous sequences containing non-proteinaceous residues. Our findings support a model in which tightly-intertwined biological dependencies of RNA and protein are reflective of a long co-evolutionary history that began with rudimentary, mutually-beneficial interactions at early stages of polypeptide and nucleic acid chemical evolution.

Mutually beneficial interactions between proto-peptides and RNA

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.