Book of Abstracts: Albany 2005
tRNA Synthetases and Establishment of the Genetic Code
In modern cells, aminoacyl tRNA synthetases establish the genetic code through aminoacylation reactions, where each amino acid is matched with its nucleotide triplet embedded in the cognate tRNA (as an anticodon). Aminoacylation activity is thought to have originated in an RNA world, where ribozymes catalyzed attachment of amino acids to RNA structures that were the progenitors of tRNAs. Aminoacyl esters that join amino acids to RNA hydroxyls are higher in energy than peptide bonds so that, once aminoacylation occurs, peptide bond formation can occur spontaneously and start the evolution of protein synthesis and development of the genetic code. X-ray crystallography, phylogenetic analyses, and structure-function experimentation has provided a plausible scenario for how the code developed through the evolution of tRNAs and tRNA synthetases. These investigations offer an explanation for the long-known two classes of tRNA synthetases, the evolution of early proteins from statistical to chemical entities, and how subtle errors by synthetases perturb the code in a way that can lead to heritable diseases.
The Skaggs Institute for Chemical Biology