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 Lee4, Kweon Yu, Nahum Sonenberg, Myung Hee Kim & Sunghoon Kim

Abstract

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-offunction 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.

Article Site: https://www.nature.com/articles/s41467-019-09086-0

Original Document: https://www.nature.com/articles/s41467-019-09086-0.pdf

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