TRNA synthetase paralogs: evolutionary links in the transition from tRNA-dependent amino acid biosynthesis to de novo biosynthesis.

Abstract

Amino acids enter into protein synthesis by virtue of their attachment to transfer RNAs. The fidelity of translation results from the summed accuracy of three distinct processes: the esterification of amino acids to their cognate tRNAs by aminoacyl-tRNA synthetases (aaRSs) (1); the binding selectivity for cognate AA-tRNA pairs by elongation factor (2); and the tRNA:mRNA decoding process mediated by the small subunit of the ribosome (3). Collectively, these processes ensure that the error frequency does not exceed, on average, ≈0.03%, and that the overall rate of protein synthesis is not unduly compromised. Although the components of the translational apparatus are highly conserved, the biosynthetic machinery responsible for producing the amino acid precursors to proteins is tremendously diverse, and the capability to produce all 20 canonical standard amino acids is not universal. This apparent contradiction presents a significant challenge to untangling the connection between amino acid and protein biosynthesis, but clarity is gradually beginning to emerge. In this issue of PNAS, Roy et al. (4) provide evidence that asparagine synthetase A (AsnA) emerged from a functional aspartyl-tRNA synthetase, and thus establish the evolutionary origin of one of the two enzymes responsible for the direct biosynthesis of the amino acid asparagine. This observation forges a new, significant link between aminoacyl-tRNA synthesis and amino acid biosynthesis. For at least some of the 20 standard amino acids, indirect pathways for amino acid biosynthesis (i.e., those occurring on the tRNA) preceded direct pathways, in which de novo biosynthesis occurs before the formation of the aminoacyl-tRNA linkage. In his original formulation of the Adaptor hypothesis, Crick (5) proposed a separate activating enzyme (aaRS) for each amino acid. The relationship is now known to be quite a bit more complex, precisely because aminoacyl-tRNA can serve as a substrate for additional transformations of the amino acid (6). The …