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Mutually stabilizing interactions between proto-peptides and RNA

114 Citations2020
Moran Frenkel‐Pinter, Jay W. Haynes, Ahmad M. Mohyeldin

This study shows that cationic proto-peptides engage in mutually stabilizing interactions with RNA, providing support for the co-evolution of these molecules.

Abstract

<jats:title>Abstract</jats:title><jats:p>The close synergy between peptides and nucleic acids in current biology is suggestive of a functional co-evolution between the two polymers. 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 interactions with RNA resulting in mutual stabilization. Cationic proto-peptides significantly increase the thermal stability of folded RNA structures. In turn, RNA increases the lifetime of a depsipeptide by &gt;30-fold. Proto-peptides containing the proteinaceous amino acids Lys, Arg, or His adjacent to backbone ester bonds generally promote RNA duplex thermal stability to a greater magnitude than do analogous sequences containing non-proteinaceous residues. Our findings support a model in which tightly-intertwined biological dependencies of RNA and protein reflect a long co-evolutionary history that began with rudimentary, mutually-stabilizing interactions at early stages of polypeptide and nucleic acid co-existence.</jats:p>