Cell-based analysis of pairwise interactions between the components of the multi-tRNA synthetase complex

Jiwon Kong, Sunghoon Kim

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Cytoplasmic aminoacyl-tRNA synthetases (ARSs) are organized into multi-tRNA synthetase complexes (MSCs), from Archaea to mammals. An evolutionary conserved role of the MSCs is enhancement of aminoacylation by forming stable associations of the ARSs and tRNAs. In mammals, a single macromolecular MSC exists, which is composed of eight cytoplasmic ARSs, for nine amino acids, and three scaffold proteins. Consequently, nearly half of aminoacyl-tRNA efflux becomes concentrated at the MSC. Stable supply of aminoacyl-tRNA to the ribosome is, therefore, considered to be a major role of the mammalian MSC. Furthermore, the mammalian MSC also serves as a reservoir for releasable components with noncanonical functions. In this study, a split-luciferase complementation system was applied to investigate the configuration of the MSC in live mammalian cells. Multiplex interconnections between the components were simplified into binary protein-protein interactions, and pairwise comparison of the interactions reconstituted a framework consistent with previous in vitro studies. Reversibility of the split-luciferase reporter binding demonstrated convertible organization of the mammalian MSC, including interferon gamma (IFNγ)-stimulated glutamyl-prolyl-tRNA synthetase 1 (EPRS1) release, as well as the cooperation with the ribosome bridged by the tRNAs. The cell-based analysis provided an improved understanding of the flexible framework of the mammalian MSC in physiological conditions.

Original languageEnglish
Pages (from-to)10476-10488
Number of pages13
JournalFASEB Journal
Issue number8
Publication statusPublished - 2020 Aug 1

Bibliographical note

Publisher Copyright:
© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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