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学科主题: 药学
题名:
Strand antagonism in RNAi: an explanation of differences in potency between intracellularly expressed siRNA and shRNA
作者: 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
发表日期: 2012-02-01
DOI: 10.1093/nar/gkr927
卷: 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
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
项目资助者: The National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China
WOS记录号: WOS:000301069400039
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65272
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
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.
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