Ronshaugen, M. et al. 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: 12.64). 01/2006; 19(24):2947-52. DOI: 10.1101/gad.1372505
Source: PubMed

ABSTRACT 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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Available from: Matthew Ronshaugen, Jul 15, 2014
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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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    ABSTRACT: Patterning and phenotypic variations of appendages in insects provide important clues on developmental genetics. In the silkworm Bombyx mori, morphological variations associated with the E complex, an analogue of the Drosophila melanogaster bithorax complex, mainly determine the shape and number of prolegs on abdominal segments. Here, we report the identification and characterization of the allele responsible for the supernumerary crescents and legs-like (ECs-l) mutant, a model derived from spontaneous mutation of the E complex, with supernumerary legs and extra crescents. Fine mapping with 1605 individuals revealed a ∼68 kb sequence in the upstream intergenic region of B. mori abdominal-A (Bmabd-A) clustered with the ECs-l locus. Quantitative real-time PCR (qRT-PCR) and Western blotting analyses disclosed a marked increase in Bmabd-A expression in the ECs-l mutant at both the transcriptional and translational levels, compared to wild-type Dazao. Furthermore, we observed ectopic expression of the Bmabd-A protein in the second abdominal segment (A2) of the ECs-l mutant. Our results collectively suggest that the 68 kb region contains important regulatory elements of the Bmabd-A gene, and provide evidence that the gene is required for limb development in abdominal segments in the silkworm.
    Insect Molecular Biology 10/2013; 22(5). DOI:10.1111/imb.12039 · 2.98 Impact Factor
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    • "). Bantam proved to mediate these functions as a direct transcriptional target of the Hippo and BMP signaling pathways, which have deeply conserved activities in controlling tissue patterning and organ size (Nolo et al., 2006; Thompson and Cohen, 2006; Oh and Irvine, 2011), and bantam loss severely impairs tissue growth and confers susceptibility to apoptosis (Hipfner et al., 2002; Brennecke et al., 2003; Jaklevic et al., 2008). As another example, deletion of Drosophila Hox locus mir-iab-4/8 exhibits spatial broadening of the Hox protein Ubx in the embryo (Bender, 2008), consistent with the striking Ubx phenocopies of haltere-towing transformation induced by ectopic miR-iab-4 and miR-iab-8 (Ronshaugen et al., 2005; Stark et al., 2008; Tyler et al., 2008). We created a genome-wide resource for conditional expression of Drosophila miRNAs using the Gal4-UAS system. "
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    ABSTRACT: microRNAs (miRNAs) are endogenous short RNAs that mediate vast networks of post-transcriptional gene regulation. Although computational searches and experimental profiling provide evidence for hundreds of functional targets for individual miRNAs, such data rarely provide clear insight into the phenotypic consequences of manipulating miRNAs in vivo. We describe a genome-wide collection of 165 Drosophila miRNA transgenes and find that a majority induced specific developmental defects, including phenocopies of mutants in myriad cell-signaling and patterning genes. Such connections allowed us to validate several likely targets for miRNA-induced phenotypes. Importantly, few of these phenotypes could be predicted from computationally predicted target lists, thus highlighting the value of whole-animal readouts of miRNA activities. Finally, we provide an example of the relevance of these data to miRNA loss-of-function conditions. Whereas misexpression of several K box miRNAs inhibited Notch pathway activity, reciprocal genetic interaction tests with miRNA sponges demonstrated endogenous roles of the K box miRNA family in restricting Notch signaling. In summary, we provide extensive evidence that misexpression of individual miRNAs often induces specific mutant phenotypes that can guide their functional study. By extension, these data suggest that the deregulation of individual miRNAs in other animals may frequently yield relatively specific phenotypes during disease conditions.
    Development 06/2012; 139(15):2821-31. DOI:10.1242/dev.079939 · 6.27 Impact Factor
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    • "For example, the thoracic Antennapedia, when ubiquitously expressed, suppresses Hox genes of the head, resulting in posterior transformation of head segments towards a thoracic identity while not affecting the abdomen — here, the effect of Antp is phenotypically suppressed by bithorax-complex genes such as Ubx (Gonzalez-Reyes et al., 1990 Gibson and Gehring, 1988 ). However, posterior prevalence occurs not only postranslationally (Plaza et al., 2008) but also at the levels of transcription (Beachy et al., 1988, Hafen et al., 1984, Appel and Sakonju, 1993, Struhl and White, 1985) and posttranscriptional regulation of mRNA abundance (Yekta et al., 2004, 2008, Woltering and Durston, 2007, Ronshaugen et al.,2005 ) (Text box 3). It can thus also potentially regulate the mRNA expression of Hox genes. "
    Embryogenesis, 04/2012; , ISBN: 978-953-51-0466-7
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