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 () and Luke J. Leman ()
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Moran Frenkel-Pinter: NSF/NASA Center for Chemical Evolution
Jay W. Haynes: NSF/NASA Center for Chemical Evolution
Ahmad M. Mohyeldin: NSF/NASA Center for Chemical Evolution
Martin C: NSF/NASA Center for Chemical Evolution
Alyssa B. Sargon: NSF/NASA Center for Chemical Evolution
Anton S. Petrov: NSF/NASA Center for Chemical Evolution
Ramanarayanan Krishnamurthy: NSF/NASA Center for Chemical Evolution
Nicholas V. Hud: NSF/NASA Center for Chemical Evolution
Loren Dean Williams: NSF/NASA Center for Chemical Evolution
Luke J. Leman: NSF/NASA Center for Chemical Evolution

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-16891-5

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