Aptamers are nucleic acid molecules which are isolated from large pools of random sequences by in vitro selection based on the ligand binding properties. RNA aptamers are of special interest for several reasons: They are excellent model systems for the study of molecular recognition processes and the structural basis of RNA function and folding. Furthermore, they may provide some insight into the processes which took place about 4 billion years ago, when the first self-replicating systems appeared on earth: the so-called RNA-world hypothesis and the origin of life. The main objective of this investigation is the 3D structural analysis of an ATP binding RNA aptamer using NMR spectroscopy. The aptamer was isolated in the laboratory of J. W. Szostak (Boston, MA). The minimum sequence which binds ATP with high affinity is an oligonucleotide of 32 residues. Binding studies with ATP and chemically modified derivatives revealed a very high specificity for ATP. The different binding properties of the derivatives showed that the adenine part of ATP interacts strongly with the RNA, whereas the triphosphate group appears to make no contacts to the RNA at all. The capability of RNA to form structures which can specifically bind ATP or other biologically important molecules with high affinity indicates that RNA can perform functions which are today carried out by proteins. A detailed knowledge of the ATP-binding RNA-fold is necessary for an understanding of the possible role of RNA in early life forms and during prebiotic evolution. Furthermore, the mechanism of the RNA-ligand interactions may serve as a model system for more complicated RNA-functions, such as ribozyme activity or self-splicing of mRNA.
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