title: Microarray analysis of Drosophila dicer-2 mutants reveals potential regulation of mitochondrial metabolism by endogenous siRNAs.
abstract: RNA interference is a eukaryotic regulatory mechanism by which small non-coding RNAs typically mediate specific silencing of their cognate genes. In Drosophila, the RNase III enzyme Dicer-2 (Dcr-2) is essential for biogenesis of endogenous small interfering RNAs (endo-siRNAs), which have been implicated in regulation of endogenous protein-coding genes. Although much is known about microRNA-based regulatory networks, the biological functions of endo-siRNAs in animals remain poorly understood. We performed gene expression profiling on Drosophila dcr-2 null mutant pupae to investigate transcriptional effects caused by a severe defect in endo-siRNA production, and found 306 up-regulated and 357 down-regulated genes with at least a twofold change in expression compared with the wild type. Most of these up-regulated and down-regulated genes were associated with energy metabolism and development, respectively. Importantly, mRNA sequences of 39% of the up-regulated genes were perfectly complementary to the sequences of previously reported endo-siRNAs, suggesting they may be direct targets of endo-siRNAs. We confirmed up-regulation of five selected genes matching endo-siRNAs and concomitant down-regulation of the corresponding endo-siRNAs in dcr-2 mutant pupae. Most of the potential endo-siRNA target genes were associated with energy metabolism, including the citric acid cycle and oxidative phosphorylation in mitochondria, implying that these are major metabolic processes directly affected by endo-siRNAs in Drosophila. Consistent with this finding, dcr-2 null mutant pupae had lower ATP content compared with controls, indicating that mitochondrial energy production is impaired in these mutants. Our data support a potential role for the endo-siRNA pathway in energy homeostasis through regulation of mitochondrial metabolism.
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea.
authors.forename: Do-Hwan
authors.initials: DH
authors.lastname: Lim
authors.forename: Langho
authors.initials: L
authors.lastname: Lee
authors.forename: Chun-Taek
authors.initials: CT
authors.lastname: Oh
authors.forename: Nam-Hoon
authors.initials: NH
authors.lastname: Kim
authors.forename: Seungwoo
authors.initials: S
authors.lastname: Hwang
authors.forename: Sung-Jun
authors.initials: SJ
authors.lastname: Han
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D046228:Microarray Analysis; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D029721:Drosophila Proteins; D034741:RNA, Small Interfering; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases