Peptides as catalysts in the RNA world

Rafal Wieczorek, Mark Dörr, Pier Luigi Luisi, Pierre-Alain Monnard

Publikation: Konferencebidrag uden forlag/tidsskriftPosterForskningpeer review


The emergence of RNA chains from prebiotic soup is considered a stumbling block in the RNA world theory (Orgel 2004). Both the activation of RNA monomers and their subsequent oligomerization is hard to achieve in accepted early Earth conditions, thus putting doubt on the prebiotic plausibility of the RNA world concept.
Contrary to RNA building blocks, amino acids form quite easily in simulated prebiotic reactions. Also, many prebiotic scenarios for condensation of amino acids into peptides have been proposed and successfully demonstrated experimentally (Rode 1999). We also have growing body of experimental evidence showing various catalytic activities associated with short chain peptides, some of them as small as dipeptides.
One such peptide, composed of only two amino acid residues; serine and histidine, was reported to exhibit broad hydrolytic activities. The dipeptide SerHis can catalyze the hydrolysis of esters, proteins and nucleic acids (Li et al. 2000).
The direction of the catalysis either toward hydrolysis or condensation is determined by thermodynamic constraints. In an aqueous medium (a general requirement for prebiotically compatible reactions), hydrolysis is thermodynamically favored over condensation. However, the thermodynamic equilibrium towards condensation can be shifted even in this environment. For example, the reverse-proteolysis in prebiotic environment has been described for SerHis (Gorlero et al. 2009). In this case, SerHis was able to condense amino acids into insoluble peptides, which in turn shifted the equilibrium to produce even more product.
In the present work we describe a prebiotically plausible system in which the SerHis dipeptide acts as catalyst for the formation of RNA oligomers from imidazole derivatives of mononucleotides. The thermodynamic shift towards condensation was achieved using water/ice eutectic phase environment (Monnard and Ziock 2008). To obtain such an environment, a reaction solution was cooled below its depressed freezing point, but above the eutectic point. Under these conditions (in our case, at a temperature of -18°C), most of the water was sequestered into ice crystals and the other reactants were up-concentrated in the remaining liquid microinclusions, thus creating an environment with low water activity in which condensation reactions can occur.
The ability of simple peptides to catalyze RNA synthesis could represent a link between prebiotic chemistry and the RNA world.
Prebiotic soup likely contained complex mixtures of various molecules. Interaction of peptides and nucleotides shows that we should give more consideration to systems chemistry approach in the origin-of-life research.

Gorlero M, Wieczorek R, Adamala K, Giorgi A, Schininà ME, Stano P, Luisi PL. (2009) Ser-His catalyses the formation of peptides and PNAs. FEBS Lett. 583(1):153-6.
Li Y, Zhao Y, Hatfield S, Wan R, Zhu Q, Li X, McMills M, Ma Y, Li J, Brown KL, He C, Liu F, Chen X. (2000) Dipeptide seryl-histidine and related oligopeptides cleave DNA, protein, and a carboxyl ester. Bioorg. Med. Chem. 8(12): 2675-80.
Monnard PA, Ziock H. (2008) Eutectic phase in water-ice: a self-assembled environment conducive to metal-catalyzed non-enzymatic RNA polymerization. Chem Biodivers. 5(8):1521-39.
Orgel LE. (2004) Prebiotic chemistry and the origin of the RNA world. Crit. Rev. Biochem. Mol. Biol. 39(2):99-123.
Rode BM. (1999) Peptides and the origin of life. Peptides 20(6): 773–786.
Publikationsdato9. jan. 2012
StatusUdgivet - 9. jan. 2012
BegivenhedOrigin of Life: Gordon Research Conference - Galveston, USA
Varighed: 8. jan. 201213. jan. 2012


KonferenceOrigin of Life: Gordon Research Conference

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