Numerous key discoveries in biology have emerged from studies of RNA (ribonucleic acid), including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.
For related information, see the articles on History of Molecular Biology and History of Genetics. For background information, see the articles on RNA and nucleic acid.
1930–1950
RNA and DNA have distinct chemical properties
When first studied in the early 1900s, the chemical and biological differences between RNA and DNA were not apparent, and they were named after the materials from which they were isolated; RNA was initially known as "yeast nucleic acid" and DNA was "thymus nucleic acid". Using diagnostic chemical tests, carbohydrate chemists showed that the two nucleic acids contained different sugars, whereupon the common name for RNA became "ribose nucleic acid". Other early biochemical studies showed that RNA was readily broken down at high pH, while DNA was stable (although denatured) in alkali. Nucleoside composition analysis showed first that RNA contained similar nucleobases to DNA, with uracil instead of thymine, and that RNA contained a number of minor nucleobase components, e.g. small amounts of pseudouridine and dimethylguanine.
Localization in cell and morphogenetic role
In 1933, while studying virgin sea urchin eggs, Jean Brachet suggested that DNA is found in cell nucleus and that RNA is present exclusively in the cytoplasm. At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH. During the 1930s, Joachim Hämmerling conducted experiments with Acetabularia in which he began to distinguish the contributions of the nucleus and the cytoplasm substances (later discovered to be DNA and mRNA, respectively) to cell morphogenesis and development.
1951–1965
Messenger RNA (mRNA) carries genetic information that directs protein synthesis
The concept of messenger RNA emerged during the late 1950s, and is associated with Crick's description of his "Central Dogma of Molecular Biology", which asserted that DNA led to the formation of RNA, which in turn led to the synthesis of proteins. During the early 1960s, sophisticated genetic analysis of mutations in the lac operon of E. coli and in the rII locus of bacteriophage T4 were instrumental in defining the nature of both messenger RNA and the genetic code. The short-lived nature of bacterial RNAs, together with the highly complex nature of the cellular mRNA population, made the biochemical isolation of mRNA very challenging. This problem was overcome in the 1960s by the use of reticulocytes in vertebrates, which produce large quantities of mRNA that are highly enriched in RNA encoding alpha- and beta-globin (the two major protein chains of hemoglobin). The first direct experimental evidence for the existence of mRNA was provided by such a hemoglobin synthesizing system.
Ribosomes make proteins
In the 1950s, results of labeling experiments in rat liver showed that radioactive amino acids were found to be associated with "microsomes" (later redefined as ribosomes) very rapidly after administration, and before they became widely incorporated into cellular proteins. Ribosomes were first visualized using electron microscopy, and their ribonucleoprotein components were identified by biophysical methods, chiefly sedimentation analysis within ultracentrifuges capable of generating very high accelerations (equivalent to hundreds of thousands times gravity). Polysomes (multiple ribosomes moving along a single mRNA molecule) were identified in the early 1960s, and their study led to an understanding of how ribosomes proceed to read the mRNA in a 5′ to 3′ direction, processively generating proteins as they do so.