Microarray analysis of Drosophila dicer-2 mutants reveals potential regulation of mitochondrial metabolism by endogenous siRNAs
- Authors
- Lim, Do-Hwan; Lee, Langho; Oh, Chun-Taek; Kim, Nam-Hoon; Hwang, Seungwoo; Han, Sung-Jun; Lee, Young Sik
- Issue Date
- 2월-2013
- Publisher
- WILEY
- Keywords
- DICER-2; DROSOPHILA; ENDOGENOUS SIRNA; MICROARRAY; RNA INTERFERENCE
- Citation
- JOURNAL OF CELLULAR BIOCHEMISTRY, v.114, no.2, pp.418 - 427
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CELLULAR BIOCHEMISTRY
- Volume
- 114
- Number
- 2
- Start Page
- 418
- End Page
- 427
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/104022
- DOI
- 10.1002/jcb.24379
- ISSN
- 0730-2312
- 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. J. Cell. Biochem. 114: 418427, 2013. (c) 2012 Wiley Periodicals, Inc.
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