The success of the RNase scaffold in the advance of biosciences and in evolution

In 1938 the new word “ribonuclease” was coined to name an enzyme capable of degrading RNA, before the name “ribonucleic acid” was accepted, as at that time RNA was still labeled YNA, for Yeast Nucleic Acid. Later, four Nobel prizes were awarded to investigators working with the “ribonuclease”, RNase A from bovine pancreas. Their work greatly advanced our knowledge of protein chemistry and biology, by producing the first complete amino acid composition and the first covalent structure of a protein, the first complete synthesis of an enzyme, and the discovery that the three-dimensional structure of a protein is dictated by its amino acid sequence. Today, well over 100 homologs of RNase A have been identified in all tetrapods, and recently in fishes. Based on the latter findings, a vertebrate RNase superfamily has been appropriately defined, with RNase A as its prototype. Thus, the success of the RNase structure and function not only in promoting the advance of biosciences, but also in evolution, has become clear. Several RNases from the superfamily are endowed with non-catalytic “special” bioactions. Among these are angiogenins, characterized by their ability to stimulate the formation of blood vessels. Recently, four RNases have been identified in Danio rerio, or zebrafish, produced as recombinant proteins, and characterized. As two of them have angiogenic activity, the hypothesis is made that the whole superfamily of vertebrate RNases evolved from early angiogenic RNases. Given the microbicidal activity of some mammalian angiogenins, and of the reported fish angiogenins, the alternative hypothesis is also discussed, that the ancestral RNases were host-defense RNases.