Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Unique domain appended to vertebrate tRNA synthetase is essential for vascular development

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Xu, X. L.
  • Shi, Y.
  • Zhang, H. M.
  • Swindell, E. C.
  • Marshall, A. G.
  • Guo, Min
  • Kishi, Shuji
  • Yang, Xiang-Lei

publication date

  • February 2012

journal

  • Nature Communications  Journal

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.

subject areas

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Aminoacylation
  • Animals
  • Blood Vessels
  • Cell Nucleus
  • Crystallography, X-Ray
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Neovascularization, Physiologic
  • Nuclear Localization Signals
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Serine-tRNA Ligase
  • Signal Transduction
  • Vascular Endothelial Growth Factor A
  • Zebrafish
  • Zebrafish Proteins
scroll to property group menus

Identity

PubMed Central ID

  • PMC3293412

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms1686

PubMed ID

  • 22353712
scroll to property group menus

Additional Document Info

start page

  • 681

volume

  • 3

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support