Wu Tongde, Zhao Yingchun, Hao Zhaojing, Zhao Hongfeng, Wang Weirong
Department of Biochemistry, School of Life Sciences, Fudan University, No. 220 Handan Road, Liren Building 106, Shanghai 200433, PR China.
Int J Biol Macromol. 2009 Aug 1;45(2):157-62. doi: 10.1016/j.ijbiomac.2009.04.021. Epub 2009 May 5.
Adar-1 gene plays an important role in the negative regulation of RNA interference. We previously showed that increased adar-1 mRNA level was associated with the rebound of gene expression after RNAi suppression. In this study, we identified a PU.1 binding site upstream from transcription start point of adar-1 gene and is essential for the promoter activity. Knockdown and over-expression of the PU.1 gene resulted in decreased and increased activity of adar-1 promoter, respectively. Our results suggest that transcription factor PU.1, could bind to the adar-1 promoter and play a key role in activating transcription of gene induced by high-dose esiRNAs.
Adar-1基因在RNA干扰的负调控中发挥重要作用。我们之前表明,adar-1 mRNA水平的升高与RNAi抑制后基因表达的反弹有关。在本研究中,我们在adar-1基因转录起始点上游鉴定出一个PU.1结合位点,它对启动子活性至关重要。PU.1基因的敲低和过表达分别导致adar-1启动子活性降低和升高。我们的结果表明,转录因子PU.1可结合到adar-1启动子上,并在高剂量esiRNAs诱导的基因转录激活中起关键作用。