The authors declare no conflicts of interest.
Microarray analysis of Drosophila dicer-2 mutants reveals potential regulation of mitochondrial metabolism by endogenous siRNAs†
Article first published online: 17 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 2, pages 418–427, February 2013
How to Cite
Lim, D.-H., Lee, L., Oh, C.-T., Kim, N.-H., Hwang, S., Han, S.-J. and Lee, Y. S. (2013), Microarray analysis of Drosophila dicer-2 mutants reveals potential regulation of mitochondrial metabolism by endogenous siRNAs. J. Cell. Biochem., 114: 418–427. doi: 10.1002/jcb.24379
- Issue published online: 17 DEC 2012
- Article first published online: 17 DEC 2012
- Accepted manuscript online: 7 SEP 2012 07:55AM EST
- Manuscript Accepted: 27 AUG 2012
- Manuscript Received: 4 MAR 2012
- National Research Foundation of Korea (NRF), Mid-Career Reseacher Program. Grant Number: 2011-0016863
- Seoul Scholarship Foundation
- Korea Research Institute of Bioscience and Biotechnology Research Initiative Program
- Korea University
- NRF, Pioneer Research Center Program. Grant Number: 2012-0000433
- ENDOGENOUS SIRNA;
- RNA INTERFERENCE
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: 418–427, 2013. © 2012 Wiley Periodicals, Inc.