A protein sensor for siRNA asymmetry
A protein sensor for siRNA asymmetry
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DOI：
10.1126/science.1102755
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发表时间：
2004-11-19
期刊：
影响因子：
56.9
通讯作者：
Zamore, PD
中科院分区：
文献类型：
--
作者：
Tomari, Y;Matranga, C;Zamore, PD
为了在RNA干扰（RNAi）途径中充当向导，小干扰RNA （sirna）必须解绕成其组成链，然后与蛋白质组装形成RNA诱导沉默复合物（RISC），催化靶信使RNA裂解。两个类似于21核苷酸siRNA链的5'端碱基配对稳定性的热力学差异决定了哪条siRNA链被组装到RISC中。我们发现，在果蝇中，Dicer-2/R2D2蛋白异源二聚体在siRNA双链上的取向决定了哪条siRNA链与核心RISC蛋白Argonaute 2结合。R2D2结合具有最大双链特征的siRNA末端，从而将异源二聚体定向在siRNA双链上。强R2D2结合需要siRNA链上的5'-磷酸，该磷酸被排除在RISC之外。因此，R2D2既是siRNA热力学不对称的蛋白质传感器，也是真正的siRNA进入RNAi途径的许可因子。
To act as guides in the RNA interference (RNAi) pathway, small interfering RNAs (siRNAs) must be unwound into their component strands, then assembled with proteins to form the RNA-induced silencing complex (RISC), which catalyzes target messenger RNA cleavage. Thermodynamic differences in the base-pairing stabilities of the 5' ends of the two similar to21-nucleotide siRNA strands determine which siRNA strand is assembled into the RISC. We show that in Drosophila, the orientation of the Dicer-2/R2D2 protein heterodimer on the siRNA duplex determines which siRNA strand associates with the core RISC protein Argonaute 2. R2D2 binds the siRNA end with the greatest double-stranded character, thereby orienting the heterodimer on the siRNA duplex. Strong R2D2 binding requires a 5'-phosphate on the siRNA strand that is excluded from the RISC. Thus, R2D2 is both a protein sensor for siRNA thermodynamic asymmetry and a licensing factor for entry of authentic siRNAs into the RNAi pathway.