Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci Journal Article


Authors: Tyler, D. M.; Okamura, K.; Chung, W. J.; Hagen, J. W.; Berezikov, E.; Hannon, G. J.; Lai, E. C.
Article Title: Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci
Abstract: Many microRNA (miRNA) loci exhibit compelling hairpin structures on both sense and antisense strands; however, the possibility that a miRNA gene might produce functional species from its antisense strand has not been examined. We report here that antisense transcription of the Hox miRNA locus mir-iab-4 generates the novel pre-miRNA hairpin mir-iab-8, which is then processed into endogenous mature miRNAs. Sense and antisense iab-4/iab-8 miRNAs are functionally distinguished by their distinct domains of expression and targeting capabilities. We find that miR-iab-8-5p, like miR-iab-4-5p, is also relevant to Hox gene regulation. Ectopic mir-iab-8 can strongly repress the Hox genes Ultrabithorax and abdominal-A via extensive arrays of conserved target sites, and can induce a dramatic homeotic transformation of halteres into wings. We generalize the antisense miRNA principle by showing that several other loci in both invertebrates and vertebrates are endogenously processed on their antisense strands into mature miRNAs with distinct seeds. These findings demonstrate that antisense transcription and processing contributes to the functional diversification of miRNA genes. © 2008 by Cold Spring Harbor Laboratory Press.
Keywords: unclassified drug; nonhuman; animals; microrna; gene expression; genetic variability; drosophila; genetic transcription; in vivo study; transcription factors; nuclear proteins; vertebrata; in situ hybridization; gene expression regulation, developmental; molecular sequence data; base sequence; gene control; models, genetic; micrornas; drosophila proteins; body patterning; rna processing, post-transcriptional; hox protein; regulatory sequences, ribonucleic acid; invertebrata; genes, homeobox; genes, insect; antisense; bx-c; homeotic gene; protein mir iab 4
Journal Title: Genes and Development
Volume: 22
Issue: 1
ISSN: 0890-9369
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2008-01-01
Start Page: 26
End Page: 36
Language: English
DOI: 10.1101/gad.1615208
PUBMED: 18172163
PROVIDER: scopus
PMCID: PMC2151012
DOI/URL:
Notes: --- - "Cited By (since 1996): 57" - "Export Date: 17 November 2011" - "CODEN: GEDEE" - "Source: Scopus"
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MSK Authors
  1. David M Tyler
    6 Tyler
  2. Eric C Lai
    159 Lai
  3. Katsutomo Okamura
    26 Okamura
  4. Weijen Chung
    9 Chung
  5. Joshua W Hagen
    7 Hagen