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

    Research output: Contribution to journalArticlepeer-review

    45 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 languageEnglish
    Pages (from-to)3079-3085
    Number of pages7
    JournalFEBS Letters
    Volume585
    Issue number19
    DOIs
    Publication statusPublished - 2011 Oct 3

    Bibliographical 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 .

    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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