Archaeal aminoacyl-tRNA synthesis: unique determinants of a universal genetic code?

Abstract

The accurate synthesis of aminoacyl-tRNAs is essential for faithful translation of the genetic code and is assumed to be one of the most highly conserved processes in biology. Recently, this dogmatic view has been called into question by the sequences of a number of archaeal genomes; for example, the genomic sequence of Methanococcus jannaschii does not contain open reading frames (ORFs) encoding homologs of the asparaginyl-, cysteinyl-, glutaminyl-, and lysyl-tRNA synthetases (l-3). Furthermore, the full complement of aminoacyl-tRNAs necessary for translation is not entirely formed by the aminoacyl-tRNA synthetases (AARS). In a significant number of cases, the AARSs activate a non-cognate amino acid, and the generation of the correct aminoacyl-tRNA pair is brought about subsequently by a second protein. The use of such pathways for the formation of Gln-tRNAG’” (via Glu-tRNAG’“) and SectRNAS”” (vin Ser-tRNAS”” ) is well documented in all the living kingdoms (4, 5). Moreover, in several Archaea, an additional aminoacyl-tRNA, Asn-tRNA*““, is also formed by transformation of a mischarged tRNA rather than by direct aminoacylation with asparaginyl-tRNA synthetase. Biochemical evidence indicates that aspartyl-tRNA synthetase initially synthesizes Asp-tRNA*““, which is subsequently converted to Asn-tRNA*“” in a distinct tRNAdependent transamidation reaction (6). The use of two-step (indirect) aminoacylation pathways for the formation of Asn-tRNA*“” and Gln-tRNAG’” in