Microarray analysis of drosophila dicer-2 mutants reveals potential regulation of mitochondrial metabolism by endogenous siRNAs

Do Hwan Lim, Langho Lee, Chun Taek Oh, Nam Hoon Kim, Seungwoo Hwang, Sung Jun Han, Youngsik Lee

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 maybe 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.

Original languageEnglish
Pages (from-to)418-427
Number of pages10
JournalJournal of Cellular Biochemistry
Volume114
Issue number2
DOIs
Publication statusPublished - 2013 Feb 1

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Microarray Analysis
Microarrays
Metabolism
Small Interfering RNA
Drosophila
Genes
Pupa
Ribonuclease III
Energy Metabolism
Small Untranslated RNA
Mitochondria
Citric Acid Cycle
Oxidative Phosphorylation
Gene Expression Profiling
RNA Interference
MicroRNAs
Gene expression
Animals
Homeostasis
Up-Regulation

Keywords

  • Dicer-2
  • Drosophila
  • Endogenous sirna
  • Microarray
  • RNA Interference

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Microarray analysis of drosophila dicer-2 mutants reveals potential regulation of mitochondrial metabolism by endogenous siRNAs. / Lim, Do Hwan; Lee, Langho; Oh, Chun Taek; Kim, Nam Hoon; Hwang, Seungwoo; Han, Sung Jun; Lee, Youngsik.

In: Journal of Cellular Biochemistry, Vol. 114, No. 2, 01.02.2013, p. 418-427.

Research output: Contribution to journalArticle

Lim, Do Hwan ; Lee, Langho ; Oh, Chun Taek ; Kim, Nam Hoon ; Hwang, Seungwoo ; Han, Sung Jun ; Lee, Youngsik. / Microarray analysis of drosophila dicer-2 mutants reveals potential regulation of mitochondrial metabolism by endogenous siRNAs. In: Journal of Cellular Biochemistry. 2013 ; Vol. 114, No. 2. pp. 418-427.
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AU - Lee, Youngsik

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AB - 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 maybe 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.

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