Seryl-tRNA Synthetases in Translation and Beyond

Abstract

Abstract:For a long time seryl-tRNA synthetases (SerRSs) stood as an archetypal, canonical aminoacyl-tRNA synthetases (aaRS), exhibiting only basic tRNA aminoacylation activity and with no moonlighting functions beyond protein biosynthesis. The picture has changed substantially in recent years after the discovery that SerRSs play an important role in antibiotic production and resistance and act as a regulatory factor in vascular development, as well as after the discovery of mitochondrial morphogenesis factor homologous to SerRS in insects. In this review we summarize the recent research results from our laboratory, which advance the understanding of seryl-tRNA synthetases and further paint the dynamic picture of unexpected SerRS activities. SerRS from archaeon Methanothermobacter thermautotrophicus was shown to interact with the large ribosomal subunit and it was postulated to contribute to a more efficient translation by the"tRNA channeling" hypothesis. Discovery of the atypical SerRS in a small number of methanogenic archaea led to the discovery of a new family of enzymes in numerous bacteria -amino acid:[carrier protein] ligases (aa:CP ligases). These SerRS homologues resigned tRNA aminoacylation activity, and instead adopted carrier proteins as the acceptors of activated amino acids. The crystal structure of the aa:CP ligase complex with the carrier protein revealed that the interactions between two macromolecules are incomparable to tRNA binding by the aaRS and consequently represent a true evolutionary invention. Kinetic investigations of SerRSs and the accuracy of amino acid selection revealed that SerRSs possess pre-transfer proofreading activity, challenging the widely accepted presumption that hydrolytic proofreading activity must reside in an additional, separate editing domain, not present in SerRSs. Finally, the plant tRNA serylation system is discussed, which is particularly interesting due to the fact that protein biosynthesis takes place in three cellular compartments: cytosol, mitochondria and chloroplasts. Plant cytosolic SerRSs showed broad tRNA Ser specificity and flexibility, unlike SerRSs from other organisms. High fidelity of SerRS dually targeted to mitochondria and chloroplasts indicated its importance in plant organellar quality control.

Expression of genes for selected plant aminoacyl-tRNA synthetases in the abiotic stress

“…Aminoacyl-tRNA synthetases are therefore housekeeping proteins that play an important role in the expression of genes to create proteins. Besides that, aaRSs may be involved in a myriad of other cellular processes exerting their noncanonical function beyond translation (Guo et al 2013, Mocibob et al 2016. It is well documented that aaRSs participate in cellular stress responses in bacteria and metazoa.…”

Arabidopsis seryl‐tRNA synthetase: the first crystal structure and novel protein interactor of plant aminoacyl‐tRNA synthetase

“…Canonical function of seryl‐tRNA synthetase (SerRS) in translation is aminoacylation of tRNA Ser with serine . In majority of organisms, but not in plants , SerRS attaches serine to the selenocysteine‐specific tRNA (tRNA Sec ) which initiates metabolic pathway that enables translational incorporation of selenocysteine into selenoproteins .…”

“…Our comprehensive and detailed research of plant SerRSs in terms of their localization, substrate recognition, and fidelity revealed new interesting insights into function of plant aaRSs . The organellar SerRS dually targeted to both mitochondria and plastids emerged as a new important player in the plant organellar protein quality control .…”

“…Seryl‐tRNA synthetases from various organisms interact with diverse proteins enabling SerRS proteins to enhance their role in translation of the genetic message or to perform alternative functions in cellular processes not directly linked to translation . Interaction of yeast SerRS with peroxisomal protein Pex21p enhances cognate tRNA binding and moderately stimulates the aminoacylation efficiency of SerRS .…”

Evolutionarily conserved cysteines in plant cytosolic seryl‐tRNA synthetase are important for its resistance to oxidation

“…Research on plant SerRSs revealed their cellular localization [11,15], substrate specificity [16][17][18][19], fidelity [20], gene expression during abiotic stress [21], and protein interactor of the cytosolic enzyme [10,22]. Arabidopsis cytosolic SerRS belongs to the bacterial type of SerRS enzymes found in most archaea, bacteria, and eukaryotes [23]. Interestingly, the discovered disulfide bond in the crystal structure of Arabidopsis SerRS (PDB ID: 6GIR) is not found at that position in the crystal structures of SerRSs whose structures have been solved until now [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39].…”