New functions of aminoacyl-tRNA synthetases beyond translation

Abstract

Over the course of evolution, eukaryotic aminoacyl-tRNA synthetases (aaRSs) progressively incorporated domains and motifs that have no essential connection to aminoacylation reactions. Their accretive addition to virtually all aaRSs correlates with the progressive evolution and complexity of eukaryotes. Based on recent experimental findings focused on a few of these additions and analysis of the aaRS proteome, we propose that they are markers for aaRS-associated functions beyond translation.

Figure 1. Domain additions to specific higher eukaryote aminoacyl-tRNA synthetases

a | Temporal appearance of ELR motif and EMAPII domain, which confer and regulate cytokine activities of TyrRSs. ELR and EMAPII were added simultaneously to TyrRSs, starting from insects. b | Temporal appearance of WHEP domain for TrpRSs. WHEP domain was found to regulate the angiostatic function of human TrpRS. c | Temporal appearance of WHEP domain for GluRS–ProRSs. Initially separated, GluRS and ProRS gained WHEP domains in nematodes and fused into one protein that is linked by a WHEP domain in higher eukaryotes.

Figure 2. Temporal elaboration of new domains for all aminoacyl-tRNA synthetases and the increasing complexity of organisms

The appearance of new domains that have been joined to eukaryote aminoacyl-tRNA synthetases is shown for specific clades, as increasingly complex organisms are presented in evolution. Each of the clades is represented by a model species for which sequence databases were complete for the tRNA synthetases. These model species are: Homo sapiens, Danio rerio, Drosophila melanogaster, Caenorhabditis elegans and Saccharomyces cerevisiae. As a result of being limited to using model species for each clade, some domains not seen in the model species may be present in other species of the same clade, as the various databases are expanded. The ensembles of all of the domain additions are clearly indicated by the increasing numbers of each new domain in tRNA synthetases and of the multi-tRNA synthetase complex (MSC)-associated proteins that first appeared in arthropodes. Note that, once a new domain is joined to a synthetase, it is irreversibly retained as the tree of life ascends.

Figure 3. Sequence extensions of human ribosomal proteins, eukaryote markers, amino acid-binding proteins, and aminoacyl-tRNA synthetases

Sequences of each of 79 human ribosomal proteins were analyzed for appended sequences (domains or short peptide motifs) in a way similar to what was done for tRNA synthetases. The sequences were organized into four groups: similar to bacterial and archaeal orthologues (0–25 amino acids); short eukaryote-specific extensions (25–80 amino acids); lower eukaryote-specific extensions (found, for example, in yeast) that are longer than 80 amino acids, but are not further extended in species higher than yeast); and higher eukaryote-specific extensions that were added only in species higher than yeast and that are longer than 80 amino acids. Percentages for each of the four groups are shown for the human proteins. A similar analysis was done on two more groups. One was a group of 16 of 17 recently identified protein markers that can be used to assemble the eukaryotic tree of life (one protein was left out because its sequence is incomplete). Most members of this group have no bacterial or archaeal orthologue. The other was a group annotated as amino acid-binding proteins (Gene Ontology Database term 0016597). After removing duplicated genes, incomplete sequences and tRNA synthetases, sixteen proteins remained and were analysed.