Yoo Jae Wook, Kim Soyoun, Lee Dong-Ki
Department of Chemistry and BK School of Molecular Science, Pohang University of Science and Technology, Hyoja-dong, Nam-gu, Pohang 790-784, Republic of Korea.
Biochem Biophys Res Commun. 2008 Feb 29;367(1):78-83. doi: 10.1016/j.bbrc.2007.12.099. Epub 2007 Dec 27.
Small-interfering RNAs (siRNAs) execute specific cellular gene silencing by exploiting the endogenous RNA interference (RNAi) pathway. Therefore, excess amounts of siRNAs can saturate cellular RNAi machineries. Indeed, some siRNAs saturate the RNA-induced silencing complex (RISC) and competitively inhibit silencing by other siRNAs. However, the molecular feature of siRNAs that specifies competition potency has been undetermined. While previous reports suggested a correlation between the competition potency and silencing efficiency of siRNAs, we found that the silencing efficiency was insufficient to explain the competition potency. Instead, we show that the nucleotide sequence of the 5'-half of the guide strand determines the competition potency of an siRNA. Our finding provides important information for understanding the mechanistic basis of competition in combinatorial RNAi treatment.
小干扰RNA（siRNA）通过利用内源性RNA干扰（RNAi）途径实现特定的细胞基因沉默。因此，过量的siRNA会使细胞RNAi机制饱和。实际上，一些siRNA会使RNA诱导沉默复合体（RISC）饱和，并竞争性抑制其他siRNA的沉默作用。然而，决定竞争能力的siRNA的分子特征尚未确定。虽然之前的报告表明siRNA的竞争能力与沉默效率之间存在相关性，但我们发现沉默效率不足以解释竞争能力。相反，我们表明引导链5'端一半的核苷酸序列决定了siRNA的竞争能力。我们的发现为理解组合RNAi治疗中竞争的机制基础提供了重要信息。
