학술논문

A threonyl-tRNA synthetase-mediated translation initiation machinery
Document Type
article
Source
Nature Communications. 10(1)
Subject
Biochemistry and Cell Biology
Biological Sciences
Genetics
1.1 Normal biological development and functioning
Underpinning research
Generic health relevance
Amino Acid Sequence
Animals
Blood Vessels
Eukaryotic Initiation Factor-4E
Eukaryotic Initiation Factor-4F
Eukaryotic Initiation Factor-4G
HEK293 Cells
Human Umbilical Vein Endothelial Cells
Humans
Mice
Inbred C57BL
Peptide Chain Initiation
Translational
Protein Binding
RNA Cap-Binding Proteins
RNA
Messenger
Species Specificity
Threonine-tRNA Ligase
Vertebrates
Zebrafish
Language
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.