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Unique domain appended to vertebrate tRNA synthetase is essential for vascular development.
Xu, Xiaoling; Shi, Yi; Zhang, Hui-Min; Swindell, Eric C; Marshall, Alan G; Guo, Min; Kishi, Shuji; Yang, Xiang-Lei.
Afiliação
  • Xu X; Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nat Commun ; 3: 681, 2012 Feb 21.
Article em En | MEDLINE | ID: mdl-22353712
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Serina-tRNA Ligase / Vasos Sanguíneos / Núcleo Celular / Proteínas de Peixe-Zebra Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Serina-tRNA Ligase / Vasos Sanguíneos / Núcleo Celular / Proteínas de Peixe-Zebra Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido