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Title 

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

Authors 

D H LimL LeeC T OhN H KimSeungwoo HwangS J HanY S Lee

Publisher 

Wiley-Blackwell

Issue Date 

2013

Citation 

Journal of Cellular Biochemistry, vol. 114, no. 2, pp. 418-427

Keywords 

Dicer-2DrosophilaEndogenous sirnaMicroarrayRNA Interference

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.

ISSN 

0730-2312

Link 

http://dx.doi.org/10.1002/jcb.24379

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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