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Esslinger, S.M., Schwalb, B., Helfer, S., Michalik, K.M., Witte, H., Maier, K.C., Martin, D., Michalke, B., Tresch, A., Cramer, P., Förstemann, K. (2013). Drosophila miR-277 controls branched-chain amino acid catabolism and affects lifespan.  RNA Biol. 10(6): 1042--1056.
FlyBase ID
FBrf0222304
Publication Type
Research paper
Abstract
Development, growth and adult survival are coordinated with available metabolic resources, ascertaining that the organism responds appropriately to environmental conditions. MicroRNAs are short (21-23 nt) regulatory RNAs that confer specificity on the RNA-induced silencing complex (RISC) to inhibit a given set of mRNA targets. We profiled changes in miRNA expression during adult life in Drosophila melanogaster and determined that miR-277 is downregulated during adult life. Molecular analysis revealed that this miRNA controls branched-chain amino acid (BCAA) catabolism and as a result it can modulate the activity of the TOR kinase, a central growth regulator, in cultured cells. Metabolite analysis in cultured cells as well as flies suggests that the mechanistic basis may be an accumulation of branched-chain α-keto-acids (BCKA), rather than BCAAs, thus avoiding potentially detrimental consequences of increased branched chain amino acid levels on e.g., translational fidelity. Constitutive miR-277 expression shortens lifespan and is synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype. Transgenic inhibition with a miRNA sponge construct also shortens lifespan, in particular on protein-rich food. Thus, optimal metabolic adaptation appears to require tuning of cellular BCAA catabolism by miR-277.
PubMed ID
PubMed Central ID
PMC3904584 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase
Comments on S2 cell line used, Förstemann.
Förstemann, 2016.4.25, Comments on S2 cell line used, Förstemann. [FBrf0232273]
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    RNA Biol.
    Title
    RNA Biology.
    Publication Year
    2004-
    ISBN/ISSN
    1547-6286 1555-8584
    Data From Reference