Unique domain appended to vertebrate tRNA synthetase is essential for vascular development

• DOI: 10.1038/ncomms1686
• Publication Date: 2012-02-21T09:26:02Z
• Authors: Xiaoling Xu; Yi Shi; Hui-Min Zhang; Eric C. Swindell; Alan G. Marshall; Min Guo; Shuji Kishi; Xiang-Lei Yang
• Keywords: Cell Nucleus; Serine-tRNA Ligase; Vascular Endothelial Growth Factor A; 0301 basic medicine; Protein Conformation; Molecular Sequence Data; Nuclear Localization Signals; Active Transport, Cell Nucleus; Neovascularization, Physiologic; Zebrafish Proteins; Crystallography, X-Ray; Article; Protein Structure, Secondary; Protein Structure, Tertiary; 03 medical and health sciences; Mutation; Animals; Blood Vessels; Humans; Aminoacylation; Amino Acid Sequence; Zebrafish; Signal Transduction

New domains were progressively added to cytoplasmic aminoacyl transfer RNA (tRNA) synthetases during evolution. One example is the UNE-S domain, appended seryl-tRNA synthetase (SerRS) in species that developed closed circulatory systems. Here we show using solution and crystal structure analyses vitro vivo functional studies harbours a robust nuclear localization signal (NLS) directing SerRS nucleus where it attenuates vascular endothelial growth factor A expression. We also mutants previously linked vasculature abnormalities either deleted NLS or have sequestered an alternative conformation. structure-based second-site mutation, designed release NLS, restored normal vasculature. Thus, essential function of development depends on UNE-S. These results are first role for tRNA synthetase-associated domain at organism level, suggest acquisition has establishment systems vertebrates. Seryl-tRNA important vasculogenesis contains unique its C-terminus. In this study, shown target protein nucleus, block expression ofvegfaand be zebrafish.