Reduced levels of Ago2 expression result in increased siRNA competition in mammalian cells.
Reduced levels of Ago2 expression result in increased siRNA competition in mammalian cells.
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降低的AGO2表达水平导致哺乳动物细胞中的siRNA竞争增加。
DOI：
10.1093/nar/gkm663
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发表时间：
2007
影响因子：
14.9
通讯作者：
Crooke, Stanley T.
中科院分区：
文献类型：
--
作者：
Vickers, Timothy A.;Lima, Walt F.;Nichols, Josh G.;Crooke, Stanley T.
利用细胞RNA干扰（RNAi）机制，小干扰RNA （sirna）的管理导致特定mrna的降解。已经证明，sirna的共同施用可能导致其中一种sirna活性的衰减。利用反义和siRNA介导的rna诱导沉默复合体（RISC）基因还原，我们发现siRNA竞争与Ago2细胞表达水平的差异相关，而其他RISC蛋白的水平对竞争没有影响。我们还表明，在某些条件下，siRNA竞争而不是细胞RISC水平的降低可能导致siRNA活性的明显降低。此外，利用siRNA竞争，我们发现RISC途径在转染后约2小时内加载并导致目标RNA的可检测切割。即使在没有新蛋白质合成的情况下，RISC通路也能够被重新加载。RISC重新加载和随后诱导可检测的新靶RNA切割，需要在初始转染后约9-12小时。
Administration of small interfering RNAs (siRNAs) leads to degradation of specific mRNAs utilizing the cellular RNA interference (RNAi) machinery. It has been demonstrated that co-administration of siRNAs may lead to attenuation of activity of one of the siRNAs. Utilizing antisense and siRNA-mediated RNA-induced silencing complex (RISC) gene reduction we show that siRNA competition is correlated with differences in the cellular expression levels of Ago2, while levels of other RISC proteins have no effect on competition. We also show that under certain conditions siRNA competition rather than reduction of cellular RISC levels may be responsible for apparent reduction in siRNA activity. Furthermore, exploiting siRNA competition, we show that the RISC pathway loads and results in detectable cleavage of the target RNA in ∼2 h after transfection. The RISC pathway is also capable of being reloaded even in the absence of new protein synthesis. RISC reloading and subsequent induction of detectable cleavage of a new target RNA, requires about 9–12 h following the initial transfection.
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影响因子：
64.8
作者：
Chendrimada, TP;Gregory, RI;Shiekhattar, R
通讯作者：
Shiekhattar, R
影响因子：
5.3
作者：
Oberdoerffer, P;Kanellopoulou, C;Rajewsky, K
通讯作者：
Rajewsky, K
DOI：
10.1073/pnas.032652399
发表时间：
2002-02-05
影响因子：
11.1
作者：
Paddison, PJ;Caudy, AA;Hannon, GJ
通讯作者：
Hannon, GJ
影响因子：
56.9
作者：
Song, JJ;Smith, SK;Joshua-Tor, L
通讯作者：
Joshua-Tor, L
影响因子：
16.8
作者：
Haley, B;Zamore, PD
通讯作者：
Zamore, PD