PUBLICATION

Loss of threonyl-tRNA synthetase-like protein Tarsl2 has little impact on protein synthesis but affects mouse development

Authors
Zeng, Q.Y., Zhang, F., Zhang, J.H., Hei, Z., Li, Z.H., Huang, M.H., Fang, P., Wang, E.D., Sun, X.J., Zhou, X.L.
ID
ZDB-PUB-230415-54
Date
2023
Source
The Journal of biological chemistry   299(5): 104704 (Journal)
Registered Authors
Sun, Xiao-Jian, Zhang, Fan
Keywords
aminoacyl-tRNA synthetase, aminoacylation, tRNA, translation
MeSH Terms
  • Amino Acyl-tRNA Synthetases*/metabolism
  • Animals
  • Mice
  • Protein Biosynthesis*
  • RNA, Transfer/metabolism
  • Threonine-tRNA Ligase*/genetics
  • Threonine-tRNA Ligase*/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed
37059185 Full text @ J. Biol. Chem.
Abstract
Aminoacyl-tRNA synthetases (aaRSs) are essential components for mRNA translation. Two sets of aaRSs are required for cytoplasmic and mitochondrial translation in vertebrates. Interestingly, TARSL2 is a recently evolved duplicated gene of TARS1 (encoding cytoplasmic threonyl-tRNA synthetase) and represents the only duplicated aaRS gene in vertebrates. Although TARSL2 retains the canonical aminoacylation and editing activities in vitro, whether it is a true tRNA synthetase for mRNA translation in vivo is unclear. In this study, we showed that Tars1 is an essential gene since homozygous Tars1 knockout mice were lethal. In contrast, when Tarsl2 was deleted in mice and zebrafish, neither the abundance nor the charging levels of tRNAThrs were changed, indicating that cells relied on Tars1 but not on Tarsl2 for mRNA translation. Furthermore, Tarsl2 deletion did not influence the integrity of the multiple tRNA synthetase complex (MSC), suggesting that Tarsl2 is a peripheral member of the MSC. Finally, we observed that Tarsl2-deleted mice exhibited severe developmental retardation, elevated metabolic capacity, and abnormal bone and muscle development after 3 weeks. Collectively, these data suggest that, despite its intrinsic activity, loss of Tarsl2 has little influence on protein synthesis but does affect mouse development.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping