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

Author

Listed:
  • Xiaoling Xu

    (The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.)

  • Yi Shi

    (The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.)

  • Hui-Min Zhang

    (Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, Florida State University, 1800 East Paul Dirac Drive, Tallahassee, Florida 32310, USA.
    Present address: Bioprocess Development, Extended Characterization, Merck Research Laboratories, Union, NJ 07083, USA.)

  • Eric C. Swindell

    (The University of Texas Medical School at Houston, 6431 Fannin Street, Houston, Texas 77030, USA.)

  • Alan G. Marshall

    (Ion Cyclotron Resonance Program, National High Magnetic Field Laboratory, Florida State University, 1800 East Paul Dirac Drive, Tallahassee, Florida 32310, USA.
    Florida State University, 95 Chieftain Way, Tallahassee, Florida 32306, USA.)

  • Min Guo

    (The Scripps Research Institute, 130 Scripps Way, Jupiter, Florida 33458, USA.)

  • Shuji Kishi

    (The Scripps Research Institute, 130 Scripps Way, Jupiter, Florida 33458, USA.)

  • Xiang-Lei Yang

    (The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.)

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.

Suggested Citation

  • Xiaoling Xu & Yi Shi & Hui-Min Zhang & Eric C. Swindell & Alan G. Marshall & Min Guo & Shuji Kishi & Xiang-Lei Yang, 2012. "Unique domain appended to vertebrate tRNA synthetase is essential for vascular development," Nature Communications, Nature, vol. 3(1), pages 1-9, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1686
    DOI: 10.1038/ncomms1686
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    Cited by:

    1. Heta Desai & Katrina H. Andrews & Kristina V. Bergersen & Samuel Ofori & Fengchao Yu & Flowreen Shikwana & Mark A. Arbing & Lisa M. Boatner & Miranda Villanueva & Nicholas Ung & Elaine F. Reed & Alexe, 2024. "Chemoproteogenomic stratification of the missense variant cysteinome," Nature Communications, Nature, vol. 15(1), pages 1-24, December.

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