Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways

Young Sik Lee, Kenji Nakahara, John W. Pham, Kevin Kim, Zhengying He, Erik J. Sontheimer, Richard W. Carthew

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916 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)69-81
Number of pages13
JournalCell
Volume117
Issue number1
DOIs
Publication statusPublished - 2004 Apr 2
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lee, Y. S., Nakahara, K., Pham, J. W., Kim, K., He, Z., Sontheimer, E. J., & Carthew, R. W. (2004). Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell, 117(1), 69-81. https://doi.org/10.1016/S0092-8674(04)00261-2