Identification of <italic>miR‐305</italic>, a microRNA that promotes aging, and its target mRNAs in <italic>Drosophila</italic>.

MicroRNAs (miRNAs) are involved in the regulation of important biological processes. Here, we describe a novel <italic>Drosophila</italic> miRNAs involved in aging. We selected eight <italic>Drosophila</italic> miRNAs, displaying high homology with seed sequences of aging‐related miRNAs characterized in other species, and investigated whether the over‐expression of these miRNAs affected aging in <italic>Drosophila</italic> adult flies. The lifespan of adults over‐expressing <italic>miR‐305</italic>, a miRNA showing high homology with <italic>miR‐239</italic> in <italic>C. elegans,</italic> was significantly shorter. Conversely, a reduction in <italic>miR‐305</italic> expression led to a longer lifespan than that in control flies. <italic>miR‐305</italic> over‐expression accelerated the impairment of locomotor activity and promoted the age‐dependent accumulation of poly‐ubiquitinated protein aggregates in the muscle, as flies aged. Thus, we show that the ectopic expression of <italic>miR‐305</italic> has a deleterious effect on aging in <italic>Drosophila</italic>. To identify the targets of <italic>miR‐305</italic>, we performed RNA‐Seq. We discovered several mRNAs encoding antimicrobial peptides and insulin‐like peptides, whose expression changed in adults upon <italic>miR‐305</italic> over‐expression. We further confirmed, by qRT‐PCR, that <italic>miR‐305</italic> over‐expression significantly decreases the mRNA levels of four antimicrobial peptides. As these mRNAs contain multiple sequences matching the seed sequence of <italic>miR‐305</italic>, we speculate that a reduction in target mRNA levels, caused by ectopic miRNA expression, promotes aging. [ABSTRACT FROM AUTHOR]