Journal
CURRENT BIOLOGY
Volume 13, Issue 9, Pages 790-795Publisher
CELL PRESS
DOI: 10.1016/S0960-9822(03)00250-1
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- NIGMS NIH HHS [GM057422] Funding Source: Medline
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MicroRNAs (miRNAs) are small regulatory RNAs that are between 21 and 25 nucleotides in length and repress gene function through interactions with target mRNAs; [1, 2]. The genomes of metazoans encode on the order of several hundred miRNAs [3], but the processes they regulate have been defined for only two in C. elegans [4, 5]. We searched for new inhibitors of apoptotic cell death by testing existing collections of P element insertion lines for their ability to enhance a small-eye phenotype associated with eye-specific expression of the Drosophila cell death activator Reaper. Here we report the identification of the Drosophila miRNA mir-14 as a cell death suppressor. Loss of mir-14 enhances Reaper-dependent cell death, whereas ectopic expression suppresses cell death induced by multiple stimuli. Animals lacking mir-14 are viable. However, they are stress sensitive and have a reduced lifespan. Mir-14 mutants have elevated levels of the apoptotic effector caspase Drice, suggesting one potential site of action. Mir-14 also regulates fat metabolism. Deletion of mir-14 results in animals with increased levels of triacylglycerol and diacylglycerol, whereas increases in mir-14 copy number have the converse effect. We discuss possible relationships between these phenotypes.
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