|ZFIN ID: ZDB-PUB-170214-321|
tRNA synthetase counteracts c-Myc to develop functional vasculature
Shi, Y., Xu, X., Zhang, Q., Fu, G., Mo, Z., Wang, G.S., Kishi, S., Yang, X.L.
|Source:||eLIFE 3: e02349 (Journal)|
|Registered Authors:||Kishi, Shuji|
|Keywords:||SIRT2, VEGFA, angiogenesis, c-Myc, seryl-tRNA synthetase, vasculature|
|PubMed:||24940000 Full text @ Elife|
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. 3:e02349.
ABSTRACTRecent 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.