Mutually Stabilizing Interactions Between Proto-Peptides and RNA

Moran Frenkel-Pinter ¹ Jay W. Haynes ¹ Ahmad M. Mohyeldin ¹ Martin C ¹ Alyssa B. Sargon ¹ Anton S. Petrov ¹ Ramanarayanan Krishnamurthy ² Nicholas V. Hud ¹ Loren Dean Williams* ¹ Luke J. Leman* ²

¹School of Chemistry & Biochemistry, NSF/NASA Center for Chemical Evolution, Georgia Institute of Technology, USA
²Department of Chemistry, The Scripps Research Institute, USA

Cooperative interactions between different types of polymers are a hallmark of extant life on Earth. However, how primordial forms of this molecular mutualism shaped chemical evolution remains an unanswered question. Here we show that cationic depsipeptides, which contain both ester and amide linkages, produced as mixtures from plausible prebiotic dry-down reactions or synthesized by chemical procedures, can engage in mutually-beneficial cooperative interactions with RNA. The cationic depsipeptides can increase the thermal stability of folded RNA structures, whereas RNA can greatly reduce the rate of hydrolysis of the backbone ester bonds in the depsipeptides. Intriguingly, proto-peptides containing the proteinaceous subset of cationic side chains generally promoted RNA duplex thermal stability to a greater magnitude than did oligomers containing non-proteinaceous cationic side chains. Thus, the tightly-intertwined biological dependencies between RNA and proteins could be reflective of a long co-evolutionary history.