Lee Young Sik, Nakahara Kenji, Pham John W, Kim Kevin, He Zhengying, Sontheimer Erik J, Carthew Richard W
Department of Biochemistry, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA.
Cell. 2004 Apr 2;117(1):69-81. doi: 10.1016/s0092-8674(04)00261-2.
The RNase III enzyme Dicer processes RNA into siRNAs and miRNAs, which direct a RNA-induced silencing complex (RISC) to cleave mRNA or block its translation (RNAi). We have characterized mutations in the Drosophila dicer-1 and dicer-2 genes. Mutation in dicer-1 blocks processing of miRNA precursors, whereas dicer-2 mutants are defective for processing siRNA precursors. It has been recently found that Drosophila Dicer-1 and Dicer-2 are also components of siRNA-dependent RISC (siRISC). We find that Dicer-1 and Dicer-2 are required for siRNA-directed mRNA cleavage, though the RNase III activity of Dicer-2 is not required. Dicer-1 and Dicer-2 facilitate distinct steps in the assembly of siRISC. However, Dicer-1 but not Dicer-2 is essential for miRISC-directed translation repression. Thus, siRISCs and miRISCs are different with respect to Dicers in Drosophila.
核糖核酸酶III（RNase III）酶Dicer将RNA加工成小干扰RNA（siRNA）和微小RNA（miRNA），这些RNA会引导RNA诱导沉默复合体（RISC）切割信使核糖核酸（mRNA）或阻断其翻译（RNA干扰）。我们已经鉴定了果蝇dicer-1和dicer-2基因中的突变。dicer-1中的突变会阻断miRNA前体的加工，而dicer-2突变体在加工siRNA前体方面存在缺陷。最近发现，果蝇Dicer-1和Dicer-2也是依赖siRNA的RISC（siRISC）的组成成分。我们发现，siRNA引导的mRNA切割需要Dicer-1和Dicer-2，不过Dicer-2的RNase III活性并非必需。Dicer-1和Dicer-2在siRISC组装过程中促进不同步骤。然而，Dicer-1对miRISC引导的翻译抑制至关重要，而Dicer-2并非如此。因此，在果蝇中，就Dicer而言，siRISC和miRISC是不同的。
