Spatial regulation of microRNA gene expression in the Drosophila embryo

Frédéric Biemar, Robert Zinzen, Matthew Ronshaugen, Victor Sementchenko, J. Robert Manak, Michael S. Levine

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

MicroRNAs (miRNAs) regulate posttranscriptional gene activity by binding to specific sequences in the 3′ UTRs of target mRNAs. A number of metazoan miRNAs have been shown to exhibit tissue-specific patterns of expression. Here, we investigate the possibility that localized expression is mediated by tissue-specific enhancers, comparable to those seen for protein-coding genes. Two miRNA loci in Drosophila melanogaster are investigated, the mir-309-5 polycistron (8-miR) and the mir-1 gene. The 8-miR locus contains a cluster of eight distinct miRNAs that are transcribed in a common precursor RNA. The 8-miR primary transcript displays a dynamic pattern of expression in early embryos, including repression at the anterior and posterior poles. An 800-bp 5′ enhancer was identified that recapitulates this complex pattern when attached to a RNA polymerase Il core promoter fused to a lacZ-reporter gene. The miR-1 locus is specifically expressed in the mesoderm of gastrulating embryos. Bioinformatics methods were used to identify a mesoderm-specific enhancer located ≈5 kb 5′ of the miR-1 transcription unit. Evidence is presented that the 8-miR enhancer is regulated by the localized Huckebein repressor, whereas miR-1 is activated by Dorsal and Twist. These results provide evidence that restricted activities of the 8-miR and miR-1 miRNAs are mediated by classical tissue-specific enhancers.

Original languageEnglish (US)
Pages (from-to)15907-15911
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number44
DOIs
StatePublished - Nov 1 2005

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Development
  • Enhancer
  • Transcription

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