Ronshaugen, M., Biemar, F., Piel, J., Levine, M. & Lai, E. C. The Drosophila microRNA iab-4 causes a dominant homeotic transformation of halteres to wings. Genes Dev. 19, 2947-2952

Department of Molecular and Cell Biology, Division of Genetics, Center for Integrative Genomics, University of California, Berkeley, 94720, USA.
Genes & Development (Impact Factor: 10.8). 01/2006; 19(24):2947-52. DOI: 10.1101/gad.1372505
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The Drosophila Bithorax Complex encodes three well-characterized homeodomain proteins that direct segment identity, as well as several noncoding RNAs of unknown function. Here, we analyze the iab-4 locus, which produces the microRNAs iab-4-5p and iab-4-3p. iab-4 is analogous to miR-196 in vertebrate Hox clusters. Previous studies demonstrate that miR-196 interacts with the Hoxb8 3' untranslated region. Evidence is presented that miR-iab-4-5p directly inhibits Ubx activity in vivo. Ectopic expression of mir-iab-4-5p attenuates endogenous Ubx protein accumulation and induces a classical homeotic mutant phenotype: the transformation of halteres into wings. These findings provide the first evidence for a noncoding homeotic gene and raise the possibility that other such genes occur within the Bithorax complex. We also discuss the regulation of mir-iab-4 expression during development.

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    • "Although canalization is most likely a systemic property, few specific molecular mechanisms have been proposed to support canalization [reviewed in (Salathia and Queitsch, 2007)]. These include buffering of genetic variability by the Hsp90 chaperone (Rutherford and Lindquist, 1998; Queitsch et al., 2002; Milton et al., 2006; Samakovli et al., 2007; Sgro et al., 2010), tissue-specific maintenance of active and repressed state of developmental genes by the Polycomb (and by analogy also the trithorax) system (Lee et al., 2005; Sawarkar and Paro, 2010; Stern et al., 2012), stabilizing negative feedback by microRNAs (Ronshaugen et al., 2005; Hornstein and Shomron, 2006; Li et al., 2009; Wu et al., 2009), and piwi-mediated silencing of transposon activity (Specchia et al., 2010; Gangaraju et al., 2011) or of existing variation (Gangaraju et al., 2011). "
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    Frontiers in Genetics 06/2014; 5:168. DOI:10.3389/fgene.2014.00168
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    • "addition, Hox-embedded microRNAs (miRNAs), such as miR-iab-4, and its antisense miRNA, miR-iab-8 (also known as miR-iab-4as), have been shown to suppress Ultrabithorax (Ubx) expression, whereas only miR-iab-8 appears to inhibit D. melanogaster abd-A expression (Ronshaugen et al., 2005; Stark et al., 2008; Tyler et al., 2008). "
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    Insect Molecular Biology 10/2013; 22(5). DOI:10.1111/imb.12039 · 2.59 Impact Factor
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    • "Misexpression of some of these miRNAs result in phenotypes similar to that of loss of Notch function. Misexpression of miR-iab-5p can repress Ubx and induce a homeotic phenotype63. However, it remains to be determined whether the corresponding miRNAs mutants will impact Notch signaling or Ubx function in vivo. "
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