8 Aminoacyl tRNA Synthetases: From the RNA World to the Theater of Proteins

The algorithm of the genetic code is a “rosetta stone” that connects the RNA World to the theatre of proteins (Fig. 1). That connection comes from the aminoacylation of RNA. The ester linkage of an aminoacyl-RNA is higher in energy than that of the peptide bond. When two aminoacyl groups are brought into close proximity, spontaneous peptide-bond formation creates a peptidyl-RNA that can continue to react with other aminoacyl-RNAs to build up a polypeptide chain linked to RNA. The aminoacylation reaction is thus at the heart of the transition from the RNA World to the theatre of proteins. For this reason, aminoacyl-tRNA synthetases (AARS) are center stage for investigations of the origins of living systems. Through catalysis of the aminoacylation reaction, these enzymes match amino acids (AA) with nucleotide triplets imbedded (as anticodons) in tRNAs. The reaction typically occurs in two steps:(1)AA+ATP+AARS→AARS(AA-AMP)+PPi(2)AARS(AA-AMP)+tRNA→AA-tRNA+AMP+AARS In the first reaction, a tightly bound aminoacyl adenylate (AA-AMP) is formed. In the second reaction, the amino acid is transferred from the bound adenylate to the tRNA to form AA-tRNA, where the amino acid is linked through an aminoacyl ester to the 3′ -end of the tRNA. It is in the second reaction (the so-called transfer reaction) that the algorithm of the code is established. Each amino acid has its own aminoacyl-tRNA synthetases, so that 20 enzymes are needed. Because of the degeneracy of the code, each amino acid has more than one tRNA isoacceptor charged by the same synthetase. The code itself...