Asymmetry in the assembly of the RNAi enzyme complex
Asymmetry in the assembly of the RNAi enzyme complex
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DOI：
10.1016/s0092-8674(03)00759-1
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发表时间：
2003-10-17
期刊：
影响因子：
64.5
通讯作者：
Zamore, PD
中科院分区：
文献类型：
--
作者：
Schwarz, DS;Hutvágner, G;Zamore, PD
RNA干扰(RNAi)的关键步骤是组装RISC，RISC是介导靶RNA切割的蛋白质-siRNA复合体。在这里，我们证明了siRNA双链的两条不能同等地组装成RISC。相反，两条siRNA链5‘端碱基对的绝对和相对稳定性决定了每条链参与RNAi途径的程度。SiRNA双链可以是功能不对称的，两条链中只有一条能够触发RNAi。不对称是一类相关的小的、单链的、非编码的RNA，microRNAs(MiRNAs)的特征。我们认为单链miRNAs最初是以siRNA样的双链形式产生的，其结构注定了一条链进入RISC，另一条链被破坏。因此，RISC组装的共同步骤对于siRNA功能和miRNA生物发生来说都是一个意想不到的不对称来源。
A key step in RNA interference (RNAi) is assembly of the RISC, the protein-siRNA complex that mediates target RNA cleavage. Here, we show that the two strands of an siRNA duplex are not equally eligible for assembly into RISC. Rather, both the absolute and relative stabilities of the base pairs at the 5' ends of the two siRNA strands determine the degree to which each strand participates in the RNAi pathway. siRNA duplexes can be functionally asymmetric, with only one of the two strands able to trigger RNAi. Asymmetry is the hallmark of a related class of small, single-stranded, noncoding RNAs, microRNAs (miRNAs). We suggest that single-stranded miRNAs are initially generated as siRNA-like duplexes whose structures predestine one strand to enter the RISC and the other strand to be destroyed. Thus, the common step of RISC assembly is an unexpected source of asymmetry for both siRNA function and miRNA biogenesis.