Key Laboratory of Freshwater Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Agriculture, Shanghai Ocean University, Shanghai 201306, China.
Biochem Biophys Res Commun. 2012 Sep 28;426(3):294-8. doi: 10.1016/j.bbrc.2012.08.029. Epub 2012 Aug 23.
The Nile tilapia represents an excellent model for osmoregulation study. Osmotic stress transcription factor 1 (OSTF1) identified in tilapia gill epithelium is a critical element of osmosensory signal transduction by means of transcriptional regulation. Thus, tight regulation of OSTF1 level is necessary for tilapia osmotic adaptation. microRNAs (miRNAs), have emerged as a crucial regulator of gene expression at post-transcriptional level. We reasoned that OSTF1 expression could be regulated by miRNAs. By bioinformatics analysis, we identified a putative miR-429 binding site in the OSTF1 mRNA. Interestingly, miR-429 is down-regulated in tilapia upon osmotic stress, consistent with OSTF1 protein up-regulation. miR-429 directly regulates OSTF1 expression by targeting its 3'-UTR, and inhibition of miR-429 substantially increases OSTF1 level in vivo. Moreover, miR-429 loss of function could influence the regulation of plasma osmolality and ion concentration responding to osmotic stress. Taken together, miR-429 is an endogenous regulator of OSTF1 expression, which participates in a regulatory circuit that allows rapid gene program transitions in response to osmotic stress.
尼罗罗非鱼是研究渗透压调节的理想模型。在罗非鱼鳃上皮细胞中鉴定出的渗透压应激转录因子 1(OSTF1)是通过转录调节进行渗透压感应信号转导的关键因素。因此,OSTF1 水平的严格调节对于罗非鱼的渗透压适应是必要的。microRNAs(miRNAs)已成为转录后水平基因表达的重要调控因子。我们推测 OSTF1 的表达可能受到 miRNAs 的调控。通过生物信息学分析,我们在 OSTF1 mRNA 中鉴定出一个推定的 miR-429 结合位点。有趣的是,在渗透压应激下,miR-429 在罗非鱼中下调,与 OSTF1 蛋白上调一致。miR-429 通过靶向其 3'UTR 直接调控 OSTF1 的表达,抑制 miR-429 可显著增加体内 OSTF1 水平。此外,miR-429 功能丧失会影响对渗透压应激的血浆渗透压和离子浓度的调节。总之,miR-429 是 OSTF1 表达的内源性调节剂,参与了一个调节回路,允许快速的基因程序转换以响应渗透压应激。