Competition potency of siRNA is specified by the 5'-half sequence of the guide strand.
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.
Yoo
Jae Wook
JW
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.
Kim
Soyoun
S
Lee
Dong-Ki
DK
D001483:Base Sequence; D001667:Binding, Competitive; D002460:Cell Line; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism*
D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex