한빛사논문
Seung Jae Jeong1,2, Shinhye Park3, Loi T. Nguyen3,4, Jungwon Hwang3, Eun-Young Lee3, Hoi-Khoanh Giong5,6,7, Jeong-Soo Lee5,6, Ina Yoon1,2, Ji-Hyun Lee1, Jong Hyun Kim1, Hoi Kyoung Kim1, Doyeun Kim1, Won Suk Yang1, Seon-Young Kim7,8, Chan Yong Lee4, Kweon Yu5,6,7, Nahum Sonenberg9,10, Myung Hee Kim3,* & Sunghoon Kim1,2,*
1 Medicinal Bioconvergence Research Center, Seoul National University, Suwon 16229, Korea. 2 College of Pharmacy, Seoul National University, Seoul 08826, Korea. 3 Infection and Immunity Research Laboratory, Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea. 4 Department of Biochemistry, Chungnam National University, Daejeon 34134, Korea. 5 Disease Target Structure Research Center, KRIBB, Daejeon 34141, Korea. 6 Dementia DTC R&D Convergence Program, Korea Institute of Science and Technology, Seoul 02792, Korea. 7 KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34141, Korea. 8 Personalized Genomic Medicine Research Center, KRIBB, Daejeon 34141, Korea. 9 Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada. 10 Rosalind and Morris Goodman Cancer Research Centre, Montreal, Quebec H3A 1A3, Canada. These authors contribute equally: Seung Jae Jeong, Shinhye Park.
*Correspondence and requests for materialsshould be addressed to M.H.K. or to S.K.
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-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.
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