tRNA synthetase counteracts c-Myc to develop functional vasculature
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 invertebr...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2014-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/02349 |
| _version_ | 1811253392057565184 |
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| author | Yi Shi Xiaoling Xu Qian Zhang Guangsen Fu Zhongying Mo George S Wang Shuji Kishi Xiang-Lei Yang |
| author_facet | Yi Shi Xiaoling Xu Qian Zhang Guangsen Fu Zhongying Mo George S Wang Shuji Kishi Xiang-Lei Yang |
| author_sort | Yi Shi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:50:13Z |
| format | Article |
| id | doaj.art-be46ac133ce34b45b3aea55ccfb186d6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:50:13Z |
| publishDate | 2014-06-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-be46ac133ce34b45b3aea55ccfb186d62022-12-22T03:24:25ZengeLife Sciences Publications LtdeLife2050-084X2014-06-01310.7554/eLife.02349tRNA synthetase counteracts c-Myc to develop functional vasculatureYi Shi0Xiaoling Xu1Qian Zhang2Guangsen Fu3Zhongying Mo4George S Wang5Shuji Kishi6Xiang-Lei Yang7Department of Chemical Physiology, The Scripps Research Institute, La Jolla, United States; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United StatesDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, United States; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United StatesDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, United States; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United StatesDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, United States; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United StatesDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, United States; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United StatesDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, United States; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United StatesDepartment of Metabolism and Aging, The Scripps Research Institute, Jupiter, United StatesDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, United States; Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, United StatesRecent 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.https://elifesciences.org/articles/02349seryl-tRNA synthetasec-MycVEGFASIRT2angiogenesisvasculature |
| spellingShingle | Yi Shi Xiaoling Xu Qian Zhang Guangsen Fu Zhongying Mo George S Wang Shuji Kishi Xiang-Lei Yang tRNA synthetase counteracts c-Myc to develop functional vasculature eLife seryl-tRNA synthetase c-Myc VEGFA SIRT2 angiogenesis vasculature |
| title | tRNA synthetase counteracts c-Myc to develop functional vasculature |
| title_full | tRNA synthetase counteracts c-Myc to develop functional vasculature |
| title_fullStr | tRNA synthetase counteracts c-Myc to develop functional vasculature |
| title_full_unstemmed | tRNA synthetase counteracts c-Myc to develop functional vasculature |
| title_short | tRNA synthetase counteracts c-Myc to develop functional vasculature |
| title_sort | trna synthetase counteracts c myc to develop functional vasculature |
| topic | seryl-tRNA synthetase c-Myc VEGFA SIRT2 angiogenesis vasculature |
| url | https://elifesciences.org/articles/02349 |
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