Downregulation of the Host Gene jigr1 by miR-92 Is Essential for Neuroblast Self-Renewal in Drosophila

PLoS Genet. 2015 May 22;11(5):e1005264. doi: 10.1371/journal.pgen.1005264. eCollection 2015 May.

Abstract

Intragenic microRNAs (miRNAs), located mostly in the introns of protein-coding genes, are often co-expressed with their host mRNAs. However, their functional interaction in development is largely unknown. Here we show that in Drosophila, miR-92a and miR-92b are embedded in the intron and 3'UTR of jigr1, respectively, and co-expressed with some jigr1 isoforms. miR-92a and miR-92b are highly expressed in neuroblasts of larval brain where Jigr1 expression is low. Genetic deletion of both miR-92a and miR-92b demonstrates an essential cell-autonomous role for these miRNAs in maintaining neuroblast self-renewal through inhibiting premature differentiation. We also show that miR-92a and miR-92b directly target jigr1 in vivo and that some phenotypes due to the absence of these miRNAs are partially rescued by reducing the level of jigr1. These results reveal a novel function of the miR-92 family in Drosophila neuroblasts and provide another example that local negative feedback regulation of host genes by intragenic miRNAs is essential for animal development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Brain / embryology
  • Brain / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation*
  • Drosophila / genetics*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Gene Expression Regulation, Developmental
  • Larva / genetics
  • Larva / metabolism
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Alignment

Substances

  • 3' Untranslated Regions
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Jigr1 protein, Drosophila
  • MIRN92 microRNA, Drosophila
  • MicroRNAs
  • RNA, Messenger