PUBLICATION
Unique domain appended to vertebrate tRNA synthetase is essential for vascular development
- Authors
- Xu, X., Yi Shi, Y., Zhang, H.-M., Swindell, E.C., Marshall, A.G., Guo, M., Kishi, S., Yang, X.-L.
- ID
- ZDB-PUB-160629-1
- Date
- 2012
- Source
- Nature communications 3: 681 (Journal)
- Registered Authors
- Kishi, Shuji, Swindell, Eric C.
- Keywords
- Biological sciences, Biochemistry, Developmental biology, Molecular biology
- MeSH Terms
-
- Active Transport, Cell Nucleus
- Amino Acid Sequence
- Aminoacylation
- Animals
- Blood Vessels/abnormalities
- Blood Vessels/cytology*
- Cell Nucleus/metabolism*
- Crystallography, X-Ray
- Humans
- Molecular Sequence Data
- Mutation
- Neovascularization, Physiologic
- Nuclear Localization Signals
- Protein Conformation
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Serine-tRNA Ligase/chemistry*
- Serine-tRNA Ligase/genetics
- Serine-tRNA Ligase/metabolism*
- Signal Transduction
- Vascular Endothelial Growth Factor A/metabolism
- Zebrafish
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 22353712 Full text @ Nat. Commun.
Citation
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.
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 systems of vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping