Global Research Laboratory for RNAi Medicine, Department of Chemistry, Sungkyunkwan University, Suwon, Republic of Korea.
Biochem Biophys Res Commun. 2010 Jul 16;398(1):92-7. doi: 10.1016/j.bbrc.2010.06.041. Epub 2010 Jun 15.
Small interfering RNAs (siRNAs) specifically knock-down target mRNAs via RNA interference (RNAi) mechanism. During this process, introduction of excess amount of exogenous siRNAs could lead to the saturation of cellular RNAi machinery. One consequence of RNAi machinery saturation is the competition between two simultaneously introduced siRNAs, during which one siRNA loses gene silencing activity. Although competition phenomena have been well characterized, the molecular and sequence features of siRNAs that specify the competition potency remain poorly understood. Here, for the first time, we performed a large-scale siRNA competition potency analysis by measuring the competition potency of 56 different siRNAs and ranking them based on their competition potency. We have also established an algorithm to predict the competition potency of siRNAs based upon the conserved sequence features of strong and weak competitor siRNAs. The present study supports our hypothesis that the competition potency of siRNAs is specified by the 5'-half antisense sequence and provides a useful guideline to design siRNAs with minimal RNAi machinery saturation.
小干扰 RNA（siRNAs）通过 RNA 干扰（RNAi）机制特异性地敲低靶 mRNA。在此过程中，过量的外源性 siRNAs 的引入可能导致细胞 RNAi 机制的饱和。RNAi 机制饱和的一个后果是两种同时引入的 siRNAs 之间的竞争，在此过程中，一种 siRNA 失去基因沉默活性。尽管竞争现象已经得到很好的描述，但指定竞争效力的 siRNAs 的分子和序列特征仍知之甚少。在这里，我们首次通过测量 56 种不同 siRNAs 的竞争效力并根据其竞争效力对它们进行排序，来进行大规模的 siRNA 竞争效力分析。我们还建立了一种基于强和弱竞争 siRNAs 的保守序列特征来预测 siRNAs 竞争效力的算法。本研究支持我们的假设，即 siRNAs 的竞争效力由 5'-半反义序列指定，并为设计最小化 RNAi 机制饱和的 siRNAs 提供了有用的指导。
