miR-1 and miR-206 target different genes to have opposing roles during angiogenesis in zebrafish embryos

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. The microRNAs miR-1 and miR-206 have identical seed sequences and have been reported to regulate angiogenesis in zebrafish by repressing VegfAa expression. Here, Lin et al. describe opposing roles of the two microRNAs in regulating VegfAa expression and therefore angiogenesis in zebrafish.