29 Noncanonical Functions of Aminoacyl-tRNA Synthetases in Translational Control

Abstract

Aminoacyl-tRNA synthetases (AARSs) are ancient enzymes, ubiquitous in the three domains of life, that catalyze the ligation of amino acids to cognate tRNAs (Ibba and Söll 2000; Ribas de Pouplana and Schimmel 2001). They are uniquely responsible for deciphering the genetic code, reading the genetic information in the tRNA anticodon, and ligating the appropriate amino acid to the terminal ribose of the conserved CCA sequence at the 3′ end of the tRNA. In most prokaryotes, there are 20 AARSs, one for each major amino acid. Lower eukaryotes have separate cytoplasmic and nuclear-encoded mitochondrial (as well as chloroplastic) AARSs (Sissler et al. 2005). In all vertebrates, and in some invertebrates, the 20 cytoplasmic AARS activities are contained in 19 proteins; the bifunctional GluProRS expresses two enzyme activities in a single polypeptide chain. All synthetases contain catalytic and tRNA anticodon recognition sites in separate domains, and belong to one of two structurally distinct classes (Ibba and Söll 2000). The 10 Class I enzymes have a Rossman fold in the active site, bind the minor groove of the tRNA acceptor stem, and aminoacylate ribose at the 2′-OH position. In contrast, the 10 Class II enzymes have an antiparallel β-sheet in the active site, bind the major groove of the acceptor stem, and aminoacylate ribose at 3′-OH. Class I and II enzymes can be further grouped into subclasses that exhibit additional structural similarities and that recognize related amino acid substrates. In vertebrate cells, 9 AARS activities in 8 enzymes (including the bifunctional GluProRS, also...