miRNA-like duplexes as RNAi triggers with improved specificity.
miRNA-like duplexes as RNAi triggers with improved specificity.
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DOI：
10.3389/fgene.2012.00127
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发表时间：
2012
影响因子：
3.7
通讯作者：
Tomari Y
中科院分区：
文献类型：
--
作者：
Betancur JG;Yoda M;Tomari Y
siRNA 双链体是 RNA 干扰最常见的触发因素，首先被加载到 Argonaute (Ago) 蛋白中，然后通过过客链裂解进行解旋，这需要 Ago 蛋白的切片活性。在哺乳动物中，四种 Ago 蛋白中只有 Ago2 具有这种切片活性。相反，miRNA/miRNA* 双链体通常包含中心错配，从而阻止切片依赖性解旋。相反，特定区域（种子和 3'-中部区域）的错配可促进四种哺乳动物 Ago 蛋白中任何一种的有效的独立于切片器的解旋。切片器依赖性和切片器无关的解旋机制都会产生包含向导的 RNA 诱导沉默复合物 (RISC)，该复合物通过切割、翻译抑制和/或脱腺苷化来沉默目标 mRNA，从而导致 mRNA 衰变。在这篇综述中，我们总结了目前对 RISC 组装途径的了解，并描述了一种合理设计人工 miRNA/miRNA* 样双链体的简单方法，并强调了其在不损害特定靶标沉默活性的情况下减少不需要的“脱靶”效应的好处。
siRNA duplexes, the most common triggers of RNA interference, are first loaded into an Argonaute (Ago) protein and then undergo unwinding via passenger strand cleavage, which requires the slicer activity of the Ago protein. In mammals, only Ago2 out of the four Ago proteins possesses such slicer activity. In contrast, miRNA/miRNA* duplexes often contain central mismatches that prevent slicer-dependent unwinding. Instead, mismatches in specific regions (seed and 3′-mid regions) promote efficient slicer-independent unwinding by any of the four mammalian Ago proteins. Both slicer-dependent and slicer-independent unwinding mechanisms produce guide-containing RNA-induced silencing complex (RISC), which silences target mRNAs by cleavage, translational repression, and/or deadenylation that leads to mRNA decay. In this review, we summarize our current knowledge of the RISC assembly pathways, and describe a simple method to rationally design artificial miRNA/miRNA*-like duplexes and highlight its benefits to reduce the unwanted “off-target” effects without compromising the specific target silencing activity.
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影响因子：
10.5
作者：
Babiarz, Joshua E.;Ruby, J. Graham;Blelloch, Robert
通讯作者：
Blelloch, Robert
影响因子：
64.5
作者：
Foerstemann, Klaus;Horwich, Michael D.;Zamore, Phillip D.
通讯作者：
Zamore, Phillip D.
影响因子：
10.5
作者：
Miyoshi, K;Tsukumo, H;Siomi, MC
通讯作者：
Siomi, MC
影响因子：
64.5
作者：
Elkayam E;Kuhn CD;Tocilj A;Haase AD;Greene EM;Hannon GJ;Joshua-Tor L
通讯作者：
Joshua-Tor L
DOI：
10.1073/pnas.0800334105
发表时间：
2008-06-10
影响因子：
11.1
作者：
Azuma-Mukai, Asuka;Oguri, Hideo;Siomi, Mikiko C.
通讯作者：
Siomi, Mikiko C.