A very short peptide composed of only two amino acid residues; Ser and His, was reported to exhibit broad hydrolytic activities. The dipeptide SerHis can catalyse the hydrolysis of esters, proteins and nucleic acids1. The ability of such a short peptide to be an efficient catalyst could be an important factor from an origin-of-life point of view. Short peptides are plausible products of prebiotic chemistry2. Consequently, they could have influenced chemical evolution on an early stage. An enzyme catalysing hydrolytic reactions can in principle be used as catalyst for condensation: the reverse reaction to hydrolysis. 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 favoured 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 SerHis3. In this case, SerHis was able to condensate amino acids into insoluble peptides, which in turn pulled the equilibrium further toward more peptide synthesis. 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 environment4. To obtain such an environment, a reaction solution is cooled below its depressed freezing point, but above the eutectic point. Under these conditions (in our case, at a temprature of -18°C), most of the water is sequestered into ice crystals and the other reactants are up-concentrated in the remaining liquid microinclusions, thus creating an environment with low water activity in which condensation reactions can occur. Successful oligomerization of RNA monomers catalysed by the SerHis dipeptide was observed in a broad range of pH, and with all four natural nucleobases. The isomeric dipeptide HisSer did not exhibit any catalytic properties thus indicating that the specific, spatial arrangement of amino acid residues in the SerHis structure is responsible for its catalytic activity. Establishing novel synthetic pathways to RNA polymerization is important, as to date no convincing prebiotic pathway has been proposed5. The ability of simple peptides to catalyse RNA synthesis could represent a link between prebiotic chemistry and the RNA world. Finally, it hints that the evolution towards enzymes could have started at a very early stage of chemical evolution. 1. 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. 2. Rode BM. (1999) Peptides and the origin of life. Peptides 20(6): 773–786. 3. 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. 4. 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. 5. Orgel LE. (2004) Prebiotic chemistry and the origin of the RNA world. Crit. Rev. Biochem. Mol. Biol. 39(2):99-123.