Yasuda, N.; Iwagami, H.; Nakanishi, E.; Nakamiya, T.; Sasaki, Y.; Murata, T., Journal of Antibiotics 1983, 36(3), 242–249. Zagorevskii, D.V.; Aldersley, M.F.; Ferris J.P., J. American Society of Mass Spectrometry 2006, 17, 1265–1270. E-mail: [email protected]edu Creating de novo Go6983 Random RNAs. Implication
for the RNA-World Anella Fabrizio Maria1,2, De Lucrezia Davide1,2, Faiella Rachel2, Chiarabelli Cristiano1,2, Luisi Pier Luigi1 1Departement of Biology, University of RomaTre, 00146 Rome, Italy; 2European Centre for Living AZD6738 molecular weight Technology, 30124Venice, Italy The RNA World hypothesis, which assumes that an RNA World preceded our contemporary DNA/RNA/protein World, has become more and more popular in the field of the origin of life (Joyce, 2002; Orgel, 2003). Despite the recent progresses made in this field, some basic questions remain unanswered: Can RNA catalyse the reaction needed for self-replication on the early Earth? Can RNA-based life achieve the metabolic sophistication needed to give birth to the protein-nucleic acid World? To tackle to these questions a number of theoretical and AZD4547 in vivo experimental
(Szostak et al., 2001; Muller, 2006) works have been carried out with the ultimate goal of re-creating an RNA World in the laboratory. Within this framework lies the “Never Born Biopolymers (NBBs)” project (Luisi et al., 2006) and in particular the “Never Born RNAs” (NBRs) project which goal is to explore the RNAs’ sequence space for catalytic functions. This project moves from the observation that the extant collection of RNA molecules is only a minor part of the all theoretically possible RNA sequences (Luisi, 2003). On the basis of these observations, the question whether functionality is a common feature or a rare result of natural selection is of the utmost importance to elucidate the role of RNA in the origin of life and to fully exploit its biological potential. In this work we report the investigation of the catalytic properties of a completely de novo library of random RNAs with the
aim to determine whether and to what extent functional RNA spontaneously occur in a random library. A random DNA library of 60 residues was designed and produced to carry out in vitro transcription and the resulting RNAs was screened to evaluate their functional properties by means of in vitro evolution (Joyce, 2004). The population of RNAs was screened for the ability buy Ixazomib of recognized a Transition State Analogue (TSA) for the protease reaction (Yamauchi et al., 2002). According to the transition state theory (Eyring, 1935; Tanaka, 2002) enzymes catalyze chemical reactions by lowering the activation energy by recognizing and binding to the transient transition state structure as it is formed during the reaction. Based on this concept, TSA are designed to closely mimic the transition states and related high-energy intermediates with regards to bond orders, lengths, and angles, as well as expanded valences, charge distribution, and geometry.