title: Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways.
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.
authors.affiliation: Department of Biochemistry, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA.
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Lee
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakahara
authors.forename: John W
authors.initials: JW
authors.lastname: Pham
authors.forename: Kevin
authors.initials: K
authors.lastname: Kim
authors.forename: Zhengying
authors.initials: Z
authors.lastname: He
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Sontheimer
authors.forename: Richard W
authors.initials: RW
authors.lastname: Carthew
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D029721:Drosophila Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases