A soluble ribonucleic acid intermediate in protein synthesis. Hoagland MB, Stephenson ML, Scott JF, Hecht LI, Zamecnik PC. J Biol Chem. 1958 Mar;231(1):241-57.

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The mechanism behind the movement of genetic information from DNA to RNA to protein is well understood and highly conserved across all domains of life. Naturally, something so widespread would be the ideal subject of scientific research. Scientists in the 1940s and 50s took it upon themselves to do just that. To do this, a method of observing protein biosynthesis in vitro was developed. Through addition of modified lab-produced amino acids containing a radioactive carbon isotope to an extracellular protein synthesis system, they were able to detect uptake of amino acid into protein. This subsequently fuelled the fire of research in this area, quickly leading to the discovery of the role of ATP in ‘activating’ amino acids prior to incorporation into protein. This, in turn, ultimately led to the discovery of a new type of RNA molecule that would bind to the radioactive amino acids and subsequently transfer them into a protein molecule, but only in the presence of GTP. What was going on here? A subsequent repetition of the experiment culminated in this final conclusion: Amino acids are activated by an enzyme and bound to a specialised RNA molecule responsible for then transferring the amino acid into protein. They also concluded that GTP was necessary to facilitate the incorporation of the amino acids into protein. This research has proven invaluable for our current understanding of genetics. Hoagland and colleagues introduced the concepts of transfer RNA (tRNA) and aminoacyl-tRNA synthetases, as well is giving us all-important hints about how the resulting polypeptide chain grows. All knowledge has to start somewhere, and the importance of understanding the science behind the most basic genetic concepts is necessary for further building our understanding of this ever-increasingly important field.

Creator: Roy Seidenkamp

References:
Demoss JA, Novelli GD. An amino acid dependent exchange between 32P labeled inorganic pyrophosphate and ATP in microbial extracts. Biochim Biophys Acta. 1956;22(1):49-61.
Hoagland MB, Keller EB, Zamecnik PC. Enzymatic carboxyl activation of amino acids. J Biol Chem. 1956;218(1):345-358.
Hoagland MB, Stephenson ML, Scott JF, Hecht LI, Zamecnik PC. A soluble ribonucleic acid intermediate in protein synthesis. J Biol Chem. 1958;231(1):241-257.
Hoagland MB, Zamecnik PC, Stephenson ML. Intermediate reactions in protein biosynthesis. Biochim Biophys Acta. 1957;24(1):215-216.
Wallin G, Kamerlin SC, Aqvist J. Energetics of activation of GTP hydrolysis on the ribosome. Nat Commun. 2013;4:1733.
Winnick T, Friedberg F, Greenberg DM. The utilization of labeled glycine in the process of amino acid incorporation by the protein of liver homogenate. J Biol Chem. 1948;175(1):117-126.
Zamecnik PC, Keller EB. Relation between phosphate energy donors and incorporation of labeled amino acids into proteins. J Biol Chem. 1954;209(1):337-354.