Mutually stabilizing interactions between proto-peptides and RNA

July 30, 2020


Mutually stabilizing interactions between proto-peptides and RNA


Moran Frenkel-Pinter, Jay W. Haynes, Ahmad M. Mohyeldin, Martin C, Alyssa B. Sargon, Anton S. Petrov, Ramanarayanan Krishnamurthy, Nicholas V. Hud, Loren Dean Williams, Luke J. Leman




Nature Communications


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 >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.




Circular dichroism, RNA structure, Ligand binding, Biochemistry