A genome-wide transgenic resource for conditional expression of Drosophila microRNAs Journal Article


Authors: Bejarano, F. ; Bortolamiol-Becet, D.; Dai, Q.; Sun, K.; Saj, A.; Chou, Y. T.; Raleigh, D. R.; Kim, K.; Ni, J. Q.; Duan, H.; Yang, J. S.; Fulga, T. A.; Van Vactor, D.; Perrimon, N.; Lai, E. C.
Article Title: A genome-wide transgenic resource for conditional expression of Drosophila microRNAs
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.
Keywords: signal transduction; genetics; phenotype; animal; metabolism; animals; microrna; biological model; gene expression profiling; models, biological; genetic association; genome-wide association study; notch receptor; physiology; gene expression regulation; receptors, notch; transgene; genome; drosophila melanogaster; micrornas; drosophila proteins; transgenes; drosophila protein; genetic database; forelimb; databases, genetic; wing; notch protein, drosophila
Journal Title: Development
Volume: 139
Issue: 15
ISSN: 0950-1991
Publisher: Company of Biologists  
Date Published: 2012-08-01
Start Page: 2821
End Page: 2831
Language: English
DOI: 10.1242/dev.079939
PUBMED: 22745315
PROVIDER: scopus
PMCID: PMC3392707
DOI/URL:
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 28 January 2013" - "Source: Scopus"
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MSK Authors
  1. Qi Dai
    13 Dai
  2. Eric C Lai
    159 Lai
  3. Abil Saj
    2 Saj
  4. Hong Duan
    12 Duan
  5. Yuting Chou
    11 Chou
  6. Jr-Shiuan Yang
    13 Yang
  7. Kailiang Sun
    6 Sun