Identification of miR-305, a microRNA that promotes aging, and its target mRNAs in Drosophila

Genes Cells. 2018 Feb;23(2):80-93. doi: 10.1111/gtc.12555. Epub 2018 Jan 5.

Abstract

MicroRNAs (miRNAs) are involved in the regulation of important biological processes. Here, we describe a novel Drosophila miRNAs involved in aging. We selected eight Drosophila 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 Drosophila adult flies. The lifespan of adults over-expressing miR-305, a miRNA showing high homology with miR-239 in C. elegans, was significantly shorter. Conversely, a reduction in miR-305 expression led to a longer lifespan than that in control flies. miR-305 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 miR-305 has a deleterious effect on aging in Drosophila. To identify the targets of miR-305, we performed RNA-Seq. We discovered several mRNAs encoding antimicrobial peptides and insulin-like peptides, whose expression changed in adults upon miR-305 over-expression. We further confirmed, by qRT-PCR, that miR-305 over-expression significantly decreases the mRNA levels of four antimicrobial peptides. As these mRNAs contain multiple sequences matching the seed sequence of miR-305, we speculate that a reduction in target mRNA levels, caused by ectopic miRNA expression, promotes aging.

Keywords: Drosophila; aging; antimicrobial peptides; microRNA; muscle.

MeSH terms

  • Aging*
  • Animals
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / physiology*
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*

Substances

  • Antimicrobial Cationic Peptides
  • Drosophila Proteins
  • MIRN305 microRNA, Drosophila
  • MicroRNAs
  • RNA, Messenger