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.
Bibliographical noteFunding 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.).
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)