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Strand antagonism in RNAi: an explanation of differences in potency between intracellularly expressed siRNA and shRNA
Jin, Xin; Sun, Tingting; Zhao, Chuanke; Zheng, Yongxiang; Zhang, Yufan; Cai, Weijing; He, Qiuchen; Taira, Kaz; Zhang, Lihe; Zhou, Demin
刊名NUCLEIC ACIDS RESEARCH
2012-02-01
DOI10.1093/nar/gkr927
40期:4页:1797-1806
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
资助者The National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; The National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]SMALL INTERFERING RNA ; SHORT HAIRPIN RNAS ; MAMMALIAN-CELLS ; LENTIVIRAL VECTORS ; GENE-EXPRESSION ; FUNCTIONAL SIRNAS ; LIBRARIES ; PROMOTER ; DELIVERY ; NUCLEAR
英文摘要

Strategies to regulate gene function frequently use small interfering RNAs (siRNAs) that can be made from their shRNA precursors via Dicer. However, when the duplex components of these siRNA effectors are expressed from their respective coding genes, the RNA interference (RNAi) activity is much reduced. Here, we explored the mechanisms of action of shRNA and siRNA and found the expressed siRNA, in contrast to short hairpin RNA (shRNA), exhibits strong strand antagonism, with the sense RNA negatively and unexpectedly regulating RNAi. Therefore, we altered the relative levels of strands of siRNA duplexes during their expression, increasing the level of the antisense component, reducing the level of the sense component, or both and, in this way we were able to enhance the potency of the siRNA. Such vector-delivered siRNA attacked its target effectively. These findings provide new insight into RNAi and, in particular, they demonstrate that strand antagonism is responsible for making siRNA far less potent than shRNA.

语种英语
所属项目编号2010CB12300 ; 20932001 ; 91029711
资助者The National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; The National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China
WOS记录号WOS:000301069400039
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被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65272
专题北京大学药学院
作者单位Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
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Jin, Xin,Sun, Tingting,Zhao, Chuanke,et al. Strand antagonism in RNAi: an explanation of differences in potency between intracellularly expressed siRNA and shRNA[J]. NUCLEIC ACIDS RESEARCH,2012,40(4):1797-1806.
APA Jin, Xin.,Sun, Tingting.,Zhao, Chuanke.,Zheng, Yongxiang.,Zhang, Yufan.,...&Zhou, Demin.(2012).Strand antagonism in RNAi: an explanation of differences in potency between intracellularly expressed siRNA and shRNA.NUCLEIC ACIDS RESEARCH,40(4),1797-1806.
MLA Jin, Xin,et al."Strand antagonism in RNAi: an explanation of differences in potency between intracellularly expressed siRNA and shRNA".NUCLEIC ACIDS RESEARCH 40.4(2012):1797-1806.
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