Unique domain appended to vertebrate tRNA synthetase is essential for vascular development
In: Nature communications, Jg. 3 (2011-10-24)
Online
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Zugriff:
New domains were progressively added to cytoplasmic aminoacyl transfer RNA (tRNA) synthetases during evolution. One example is the UNE-S domain, appended to seryl-tRNA synthetase (SerRS) in species that developed closed circulatory systems. Here we show using solution and crystal structure analyses and in vitro and in vivo functional studies that UNE-S harbours a robust nuclear localization signal (NLS) directing SerRS to the nucleus where it attenuates vascular endothelial growth factor A expression. We also show that SerRS mutants previously linked to vasculature abnormalities either deleted the NLS or have the NLS sequestered in an alternative conformation. A structure-based second-site mutation, designed to release the sequestered NLS, restored normal vasculature. Thus, the essential function of SerRS in vascular development depends on UNE-S. These results are the first to show an essential role for a tRNA synthetase-associated appended domain at the organism level, and suggest that acquisition of UNE-S has a role in the establishment of the closed circulatory systems of vertebrates.
Seryl-tRNA synthetase is important in vasculogenesis and contains a unique domain at its C-terminus. In this study, the unique domain is shown to target the protein to the nucleus, block expression of vegfa and be essential for vasculogenesis in zebrafish.
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Unique domain appended to vertebrate tRNA synthetase is essential for vascular development
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Autor/in / Beteiligte Person: | Yang, Xiang-Lei ; Marshall, Alan G. ; Shi, Yi ; Swindell, Eric C. ; Zhang, Hui-Min ; Xu, Xiaoling ; Kishi, Shuji ; Guo, Min |
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Zeitschrift: | Nature communications, Jg. 3 (2011-10-24) |
Veröffentlichung: | 2011 |
Medientyp: | unknown |
ISSN: | 2041-1723 (print) |
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