Sun Lei, Li Heng, Xu Xiaofeng, Xiao Guanxiu, Luo Chen
a College of Life Sciences; Zhejiang University ; Hangzhou , Zhejiang , China.
RNA Biol. 2015;12(6):615-27. doi: 10.1080/15476286.2015.1034919.
MicroRNAs are major post-transcriptional regulators of gene expression and have essential roles in diverse developmental processes. In vertebrates, some regulatory genes play different roles at different developmental stages. These genes are initially transcribed in a wide embryonic region but restricted within distinct cell types at subsequent stages during development. Therefore, post-transcriptional regulation is required for the transition from one developmental stage to the next and the establishment of different cell identities. However, the regulation of many multiple functional genes at post-transcription level during development remains unknown. Here we show that miR-20a can target the mRNA of vsx1, a multiple functional gene, at the 3'-UTR and inhibit protein expression in both goldfish and zebrafish. The expression of miR-20a is initiated ubiquitously at late gastrula stage and exhibits a tissue-specific pattern in the developing retina. Inhibition of vsx1 3'-UTR mediated protein expression occurs when and where miR-20a is expressed. Decoying miR-20a resulted in severely impaired head, eye and trunk formation in association with excessive generation of vsx1 marked neurons in the spinal cord and defects of somites in the mesoderm region. These results demonstrate that miR-20a is essential for normal embryogenesis by restricting Vsx1 expression in goldfish and zebrafish, and that post-transcriptional regulation is an essential mechanism for Vsx1 playing different roles in diverse developmental processes.
微小RNA是基因表达的主要转录后调节因子,在多种发育过程中发挥着重要作用。在脊椎动物中,一些调节基因在不同的发育阶段发挥不同的作用。这些基因最初在广泛的胚胎区域转录,但在发育的后续阶段局限于不同的细胞类型中。因此,从一个发育阶段过渡到下一个阶段以及建立不同的细胞身份需要转录后调节。然而,在发育过程中许多多功能基因在转录后水平的调节仍不清楚。在这里,我们表明miR-20a可以靶向多功能基因vsx1的mRNA的3'-UTR,并在金鱼和斑马鱼中抑制蛋白质表达。miR-20a的表达在原肠胚后期开始普遍出现,并在发育中的视网膜中呈现组织特异性模式。当且在miR-20a表达的地方,会发生对vsx1 3'-UTR介导的蛋白质表达的抑制。诱捕miR-20a会导致头部、眼睛和躯干形成严重受损,同时脊髓中标记有vsx1的神经元过度生成以及中胚层区域的体节缺陷。这些结果表明,miR-20a通过限制金鱼和斑马鱼中Vsx1的表达对正常胚胎发生至关重要,并且转录后调节是Vsx1在不同发育过程中发挥不同作用的重要机制。