Identification of sequence features that predict competition potency of siRNAs.
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.
Li
Xin
X
Global Research Laboratory for RNAi Medicine, Department of Chemistry, Sungkyunkwan University, Suwon, Republic of Korea.
Yoo
Jae Wook
JW
Lee
June Hyung
JH
Hahn
Yoonsoo
Y
Kim
Soyoun
S
Lee
Dong-Ki
DK
D001483:Base Sequence; D001667:Binding, Competitive; D016384:Consensus Sequence; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics*; D017423:Sequence Analysis, RNA
D015852:Eukaryotic Initiation Factor-2; D034741:RNA, Small Interfering