A threonyl-tRNA synthetase-mediated translation initiation machinery

Seung Jae Jeong, Shinhye Park, Loi T. Nguyen, Jungwon Hwang, Eun Young Lee, Hoi Khoanh Giong, Jeong Soo Lee, Ina Yoon, Ji Hyun Lee, Jong Hyun Kim, Hoi Kyoung Kim, Doyeun Kim, Won Suk Yang, Seon Young Kim, Chan Yong Lee, Kweon Yu, Nahum Sonenberg, Myung Hee Kim, Sunghoon Kim

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


A fundamental question in biology is how vertebrates evolved and differ from invertebrates, and little is known about differences in the regulation of translation in the two systems. Herein, we identify a threonyl-tRNA synthetase (TRS)-mediated translation initiation machinery that specifically interacts with eIF4E homologous protein, and forms machinery that is structurally analogous to the eIF4F-mediated translation initiation machinery via the recruitment of other translation initiation components. Biochemical and RNA immunoprecipitation analyses coupled to sequencing suggest that this machinery emerged as a gain-of-function event in the vertebrate lineage, and it positively regulates the translation of mRNAs required for vertebrate development. Collectively, our findings demonstrate that TRS evolved to regulate vertebrate translation initiation via its dual role as a scaffold for the assembly of initiation components and as a selector of target mRNAs. This work highlights the functional significance of aminoacyl-tRNA synthetases in the emergence and control of higher order organisms.

Original languageEnglish
Article number1357
JournalNature communications
Issue number1
Publication statusPublished - 2019 Dec 1

Bibliographical note

Funding Information:
We thank beamline staff at the Photon Factory, Japan (BL-5A, BL-17A) and Pohang Light Source, Korea (BL-5C) for assistance during X-ray diffraction experiments, and Dr. Jong Hwan Kim at KRIBB for initial processing of mRNA sequencing data. This study was supported by the National Research Foundation of Korea, funded by the Ministry of Science and ICT of Korea (NRF-M3A6A4–2010–0029785 to S.K.; NRF-2010–0029767 to M.H.K.), and the KRIBB Initiative Program (M.H.K.).

Publisher Copyright:
© 2019, The Author(s).

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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