DMCA
Unique domain appended to vertebrate tRNA synthetase is essential for vascular development
| Citations: | 7 - 2 self |
BibTeX
@MISC{Xu_uniquedomain,
author = {Xiaoling Xu and Yi Shi and Hui-min Zhang and Eric C. Swindell and Alan G. Marshall and Min Guo and Shuji Kishi and Xiang-lei Yang},
title = {Unique domain appended to vertebrate tRNA synthetase is essential for vascular development},
year = {}
}
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Abstract
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
Keyphrases
vascular development unique domain trna synthetase organism level seryl-trna synthetase vivo functional study essential role closed circulatory une-s domain structure-based second-site mutation essential function new domain vascular endothelial growth factor crystal structure analysis sequestered nls alternative conformation circulatory system robust nuclear localization signal normal vasculature aminoacyl transfer rna
