The RNAs were an undeniable reality: rRNA, tRNA, and finally the ephemeral mRNA; they had moved to the center stage of molecular biology. However, the process of their synthesis was still awaiting elucidation. Jacob and Monod did not even care to admit the existence of a problem. This issue was taken up by the classical biochemists, typifying an era whose pinnacle had already passed. Many of these scientists were quite accessible to new challenges coming from molecular biology — they were, actually, too smart to react otherwise, contradicting insinuations concocted by some of the new heroes of molecular genetics. The biochemists’ main field of action, where their visceral main interest lay, were the classical problems of metabolism (where does the energy come from?), the enzymes. Epitomizing that school of thought, R.M.S. Smellie at the University of Glasgow, one of the pioneers in RNA synthesis, published a review which starts out with a never ending reflection on the synthesis of nucleotide building blocks: “The reaction sequence... involves the reaction of carbamyl phosphate with CO2 and glutamate to yield ureidosuccinic acid, ring closure to form dihydroorotic acid, and oxidation to form orotic acid, which then reacts with phosphoribosyl pyrophosphate to give orotidine 5’-monophosphate. 5’UMP is formed from orotidine 5’-monophosphate by decarboxylation and the cytidine nucleotides are derived from the uridine nucleotides by amination...”. And beyond all these details, there were systems in which one or two nucleotides were attached to RNA molecules. All these themes spoke directly to biochemists and warmed their hearts....but where were the concerns for the problems of information transfer hidden? Politely mentioned, yes — but merely at the end of the 30-pages text: ...it is postulated that during the assemblage of a protein molecule, amino acids, coupled to sRNA, are transferred to a template, most probably an RNA molecule associated to a ribosome (Smellie, 1963).
KeywordsOrotic Acid Carbamyl Phosphate Phosphoribosyl Pyrophosphate Uridine Nucleotide Core Polymerase
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