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Shi Y, Xu X, Zhang Q, et al. tRNA synthetase counteracts c-Myc to develop functional vasculature. Elife. 2014;3:e02349doi: 10.7554/eLife.02349.
Shi, Y., Xu, X., Zhang, Q., Fu, G., Mo, Z., Wang, G. S., Kishi, S., & Yang, X. L. (2014). tRNA synthetase counteracts c-Myc to develop functional vasculature. eLife, 3e02349. https://doi.org/10.7554/eLife.02349
Shi, Yi, et al. "tRNA synthetase counteracts c-Myc to develop functional vasculature." eLife vol. 3 (2014): e02349. doi: https://doi.org/10.7554/eLife.02349
Shi Y, Xu X, Zhang Q, Fu G, Mo Z, Wang GS, Kishi S, Yang XL. tRNA synthetase counteracts c-Myc to develop functional vasculature. Elife. 2014 Jun 17;3:e02349. doi: 10.7554/eLife.02349. PMID: 24940000; PMCID: PMC4057782.
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Elife. 2014 Jun 17;3:e02349. doi: 10.7554/eLife.02349.

tRNA synthetase counteracts c-Myc to develop functional vasculature.

eLife

Yi Shi, Xiaoling Xu, Qian Zhang, Guangsen Fu, Zhongying Mo, George S Wang, Shuji Kishi, Xiang-Lei Yang

Affiliations

  1. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, United States Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States.
  2. Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, United States.
  3. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, United States Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United States [email protected].

PMID: 24940000 PMCID: PMC4057782 DOI: 10.7554/eLife.02349

Abstract

Recent studies suggested an essential role for seryl-tRNA synthetase (SerRS) in vascular development. This role is specific to SerRS among all tRNA synthetases and is independent of its well-known aminoacylation function in protein synthesis. A unique nucleus-directing domain, added at the invertebrate-to-vertebrate transition, confers this novel non-translational activity of SerRS. Previous studies showed that SerRS, in some unknown way, controls VEGFA expression to prevent vascular over-expansion. Using in vitro, cell and animal experiments, we show here that SerRS intervenes by antagonizing c-Myc, the major transcription factor promoting VEGFA expression, through a tandem mechanism. First, by direct head-to-head competition, nuclear-localized SerRS blocks c-Myc from binding to the VEGFA promoter. Second, DNA-bound SerRS recruits the SIRT2 histone deacetylase to erase prior c-Myc-promoted histone acetylation. Thus, vertebrate SerRS and c-Myc is a pair of 'Yin-Yang' transcriptional regulator for proper development of a functional vasculature. Our results also discover an anti-angiogenic activity for SIRT2.DOI: http://dx.doi.org/10.7554/eLife.02349.001.

Copyright © 2014, Shi et al.

Keywords: SIRT2; VEGFA; angiogenesis; c-Myc; seryl-tRNA synthetase; vasculature

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