Mutually stabilizing interactions between proto-peptides and RNA

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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.

Original languageAmerican English
Article number3137
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - 1 Dec 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

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