1] Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan [2].
Nat Commun. 2013;4:2829. doi: 10.1038/ncomms3829.
As miR-1 and miR-206 share identical seed sequences, they are commonly speculated to target the same gene. Here, we identify an mRNA encoding seryl-tRNA synthetase (SARS), which is targeted by miR-1, but refractory to miR-206. SARS is increased in miR-1-knockdown embryos, but it remains unchanged in the miR-206 knockdown. Either miR-1 knockdown or sars overexpression results in a failure to develop some blood vessels and a decrease in vascular endothelial growth factor Aa (VegfAa) expression. In contrast, sars knockdown leads to an increase of VegfAa expression and abnormal branching of vessels, similar to the phenotypes of vegfaa-overexpressed embryos, suggesting that miR-1 induces angiogenesis by repressing SARS. Unlike the few endothelial cells observed in the miR-1-knockdown embryos, knockdown of miR-206 leads to abnormal branching of vessels accompanied by an increase in endothelial cells and VegfAa. Therefore, we propose that miR-1 and miR-206 target different genes and thus have opposing roles during embryonic angiogenesis in zebrafish.
miR-1 和 miR-206 共享相同的种子序列，因此人们普遍推测它们靶向相同的基因。在这里，我们鉴定出一种编码丝氨酰-tRNA 合成酶 (SARS) 的 mRNA，它是 miR-1 的靶标，但对 miR-206 具有抗性。miR-1 敲低的胚胎中 SARS 增加，但 miR-206 敲低的胚胎中不变。miR-1 敲低或 sars 过表达都会导致一些血管无法发育，血管内皮生长因子 Aa (VegfAa) 的表达减少。相比之下，sars 敲低会导致 VegfAa 表达增加和血管分支异常，类似于 Vegfaa 过表达胚胎的表型，表明 miR-1 通过抑制 SARS 诱导血管生成。与在 miR-1 敲低胚胎中观察到的少数内皮细胞不同，miR-206 的敲低会导致血管分支异常，同时内皮细胞和 VegfAa 增加。因此，我们提出 miR-1 和 miR-206 靶向不同的基因，因此在斑马鱼胚胎血管生成中具有相反的作用。
