|ZFIN ID: ZDB-PUB-160629-1|
Unique domain appended to vertebrate tRNA synthetase is essential for vascular development
Xu, X., Yi Shi, Y., Zhang, H.-M., Swindell, E.C., Marshall, A.G., Guo, M., Kishi, S., Yang, X.-L.
|Source:||Nature communications 3: 681 (Journal)|
|Registered Authors:||Kishi, Shuji, Swindell, Eric C.|
|Keywords:||Biological sciences, Biochemistry, Developmental biology, Molecular biology|
|PubMed:||22353712 Full text @ Nat. Commun.|
Xu, X., Yi Shi, Y., Zhang, H.-M., Swindell, E.C., Marshall, A.G., Guo, M., Kishi, S., Yang, X.-L. (2012) Unique domain appended to vertebrate tRNA synthetase is essential for vascular development. Nature communications. 3:681.
ABSTRACTNew 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.