From DNA Melting Profiles to tRNA Crystals and RNA Chaperones: How the Secondary and Tertiary Structures of Ribonucleic Acids Were Discovered—A Personal Recollection

Abstract

The secondary structure of DNA was elaborated in a quantum leap to the double helix (Watson and Crick 1953a), made possible by the confluence of chemical and fiber diffraction data. At that point, some believed that this would almost immediately lead to solution of the essential structural features of RNA. Because of the greater inherent complexity and biological versatility of RNA molecules, however, it was to take another seven years and better understanding of the properties of DNA itself before a generic model for the secondary structure of RNA could be provided (Fresco et al. 1960), and six additional years before it could be said that tRNAs are endowed with tertiary structure (Fresco et al. 1966). This chapter records my recollections of how awareness and understanding of the secondary and tertiary structures of ribonucleic acids in solution emerged. MY EARLY INTEREST IN RNA I became aware of the existence of RNA in the fall of 1947, while doing background reading for my master’s thesis on cytochemical studies of nucleic acids (Fresco et al. 1948). Although DNA was in the minds of some the repository of genes, it nevertheless seemed less interesting because it had no apparent active physiology other than in the course of cell division. RNA, on the other hand, had an active physiology, which according to the work of Caspersson (1941) and Spiegelman and Kamen (1947) was in some unknown way linked to the mysterious process of protein synthesis. This conviction that DNA is a dormant bank for...