The endogenous siRNA pathway in Drosophila impacts stress resistance and lifespan by regulating metabolic homeostasis

Do Hwan Lim; Chun Taek Oh; Langho Lee; Jae Sang Hong; Su Hyun Noh; Seungwoo Hwang; Sungchan Kim; Sung Jun Han; Young Sik Lee

doi:10.1016/j.febslet.2011.08.034

The endogenous siRNA pathway in Drosophila impacts stress resistance and lifespan by regulating metabolic homeostasis

Do Hwan Lim, Chun Taek Oh, Langho Lee, Jae Sang Hong, Su Hyun Noh, Seungwoo Hwang, Sungchan Kim, Sung Jun Han, Young Sik Lee

Division of Biotechnology

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

Abstract

Small non-coding RNAs regulate gene expression in a sequence-specific manner. In Drosophila, Dicer-2 (Dcr-2) functions in the biogenesis of endogenous small interfering RNAs (endo-siRNAs). We identified 21 distinct proteins that exhibited a ≥1.5-fold change as a consequence of loss of dcr-2 function. Most of these were metabolic genes implicated in stress resistance and aging. dcr-2 Mutants had reduced lifespan and were hypersensitive to oxidative, endoplasmic reticulum, starvation, and cold stresses. Furthermore, loss of dcr-2 function led to abnormal lipid and carbohydrate metabolism. Our results suggest roles for the endo-siRNA pathway in metabolic regulation and defense against stress and aging in Drosophila.

Original language	English
Pages (from-to)	3079-3085
Number of pages	7
Journal	FEBS Letters
Volume	585
Issue number	19
DOIs	https://doi.org/10.1016/j.febslet.2011.08.034
Publication status	Published - 2011 Oct 3

Keywords

Dicer-2
Drosophila
Endogenous siRNA
Lifespan
Metabolic homeostasis
Stress response

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2011.08.034

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title = "The endogenous siRNA pathway in Drosophila impacts stress resistance and lifespan by regulating metabolic homeostasis",

abstract = "Small non-coding RNAs regulate gene expression in a sequence-specific manner. In Drosophila, Dicer-2 (Dcr-2) functions in the biogenesis of endogenous small interfering RNAs (endo-siRNAs). We identified 21 distinct proteins that exhibited a ≥1.5-fold change as a consequence of loss of dcr-2 function. Most of these were metabolic genes implicated in stress resistance and aging. dcr-2 Mutants had reduced lifespan and were hypersensitive to oxidative, endoplasmic reticulum, starvation, and cold stresses. Furthermore, loss of dcr-2 function led to abnormal lipid and carbohydrate metabolism. Our results suggest roles for the endo-siRNA pathway in metabolic regulation and defense against stress and aging in Drosophila.",

keywords = "Dicer-2, Drosophila, Endogenous siRNA, Lifespan, Metabolic homeostasis, Stress response",

author = "Lim, {Do Hwan} and Oh, {Chun Taek} and Langho Lee and Hong, {Jae Sang} and Noh, {Su Hyun} and Seungwoo Hwang and Sungchan Kim and Han, {Sung Jun} and Lee, {Young Sik}",

note = "Funding Information: We thank R. Carthew, G. Hannon, Q. Liu, M. Siomi, and A. Lambertsson for antibodies and Drosophila strains, and the Developmental Studies Hybridoma Bank for antibodies. D.H. Lim was supported by a Hi Seoul Science/Humanities Fellowship from Seoul Scholarship Foundation. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (KRF-2008-313-C00640 to Y.S. Lee), by Brain Korea 21 Project from the Ministry of Education, Science, and Technology of Korea (to Korea University), and by KOBIC Research Support Program . ",

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volume = "585",

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AU - Lim, Do Hwan

AU - Oh, Chun Taek

AU - Lee, Langho

AU - Hong, Jae Sang

AU - Noh, Su Hyun

AU - Hwang, Seungwoo

AU - Kim, Sungchan

AU - Han, Sung Jun

AU - Lee, Young Sik

N1 - Funding Information: We thank R. Carthew, G. Hannon, Q. Liu, M. Siomi, and A. Lambertsson for antibodies and Drosophila strains, and the Developmental Studies Hybridoma Bank for antibodies. D.H. Lim was supported by a Hi Seoul Science/Humanities Fellowship from Seoul Scholarship Foundation. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (KRF-2008-313-C00640 to Y.S. Lee), by Brain Korea 21 Project from the Ministry of Education, Science, and Technology of Korea (to Korea University), and by KOBIC Research Support Program .

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Y1 - 2011/10/3

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AB - Small non-coding RNAs regulate gene expression in a sequence-specific manner. In Drosophila, Dicer-2 (Dcr-2) functions in the biogenesis of endogenous small interfering RNAs (endo-siRNAs). We identified 21 distinct proteins that exhibited a ≥1.5-fold change as a consequence of loss of dcr-2 function. Most of these were metabolic genes implicated in stress resistance and aging. dcr-2 Mutants had reduced lifespan and were hypersensitive to oxidative, endoplasmic reticulum, starvation, and cold stresses. Furthermore, loss of dcr-2 function led to abnormal lipid and carbohydrate metabolism. Our results suggest roles for the endo-siRNA pathway in metabolic regulation and defense against stress and aging in Drosophila.

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KW - Drosophila

KW - Endogenous siRNA

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KW - Metabolic homeostasis

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The endogenous siRNA pathway in Drosophila impacts stress resistance and lifespan by regulating metabolic homeostasis

Abstract

Keywords

ASJC Scopus subject areas

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