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Cited by 3,597MicroRNA in disease regulationPlant Molecular Biology ResearchRNA Research and Splicing

MicroRNA targets in Drosophila

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Enright, Anton J, John, Bino, Gaul, Ulrike, Tuschl, Thomas, Sander, Chris, Marks, Debora S·2003·Genome Biology
DOI 10.1186/gb-2003-5-1-r1PMC PMC395733
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Abstract

BACKGROUND: The recent discoveries of microRNA (miRNA) genes and characterization of the first few target genes regulated by miRNAs in Caenorhabditis elegans and Drosophila melanogaster have set the stage for elucidation of a novel network of regulatory control. We present a computational method for whole-genome prediction of miRNA target genes. The method is validated using known examples. For each miRNA, target genes are selected on the basis of three properties: sequence complementarity using a position-weighted local alignment algorithm, free energies of RNA-RNA duplexes, and conservation of target sites in related genomes. Application to the D. melanogaster, Drosophila pseudoobscura and Anopheles gambiae genomes identifies several hundred target genes potentially regulated by one or more known miRNAs. RESULTS: These potential targets are rich in genes that are expressed at specific developmental stages and that are involved in cell fate specification, morphogenesis and the coordination of developmental processes, as well as genes that are active in the mature nervous system. High-ranking target genes are enriched in transcription factors two-fold and include genes already known to be under translational regulation. Our results reaffirm the thesis that miRNAs have an important role in establishing the complex spatial and temporal patterns of gene activity necessary for the orderly progression of development and suggest additional roles in the function of the mature organism. In addition the results point the way to directed experiments to determine miRNA functions. CONCLUSIONS: The emerging combinatorics of miRNA target sites in the 3' untranslated regions of messenger RNAs are reminiscent of transcriptional regulation in promoter regions of DNA, with both one-to-many and many-to-one relationships between regulator and target. Typically, more than one miRNA regulates one message, indicative of cooperative translational control. Conversely, one miRNA may have several target genes, reflecting target multiplicity. As a guide to focused experiments, we provide detailed online information about likely target genes and binding sites in their untranslated regions, organized by miRNA or by gene and ranked by likelihood of match. The target prediction algorithm is freely available and can be applied to whole genome sequences using identified miRNA sequences.

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  • Several D. melanogaster genes with predicted miRNA target sites have HCEs in their 3' UTRs, such as the Hox cluster genes Abd-B, Antp, Scr, and Ubx.

    “We also found several examples of D. melanogaster genes with predicted miRNA target sites and HCEs in their 3Ј UTRs, such as the Hox cluster genes Abd-B, Antp, Scr, and Ubx (Enright et al. 2003).”

    From Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005) · cites this paper as Enright et al. 2003

    The Results section ('Hox genes and body axis specification'; page unavailable) predicts miRNA targeting of Hox genes, explicitly including Scr and Abd-B, and says all three Bithorax-complex genes are likely targets. The paper also requires conservation of predicted target sites, but the passages do not establish that the named genes have HCEs in their 3′ UTRs; conservation under its prediction criteria is not the same as identifying HCEs. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Enright, A. J., John, B., Gaul, U., Tuschl, T., Sander, C., & Marks, D. S.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Rockefeller University (US)
  • Columbia University (US)
Corresponding author
  • Sander, Chris
  • Marks, Debora S
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2003-12-12
Volume
5
Issue
1
Pages
R1-R1
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/gb-2003-5-1-r1
PMC
PMC395733
OpenAlex
W2120456037
Cited by
3,597
References
5
Citations by year
2026: 123 · 2025: 176 · 2024: 232 · 2023: 227 · 2022: 318 · 2021: 247 · 2020: 258 · 2019: 201 · 2018: 201 · 2017: 199 · 2016: 190 · 2015: 124 · 2014: 148 · 2013: 139 · 2012: 139
FWCI
22.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion)
  • PubMed Central (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
microRNA, miRNA target prediction, Drosophila melanogaster, Drosophila pseudoobscura, Anopheles gambiae, sequence complementarity, 3' untranslated region, translational regulation, transcription factors, developmental gene regulation
MeSH terms
Animals, Drosophila melanogaster, Ecdysone, Genes, Homeobox, Nervous System, Predictive Value of Tests, Signal Transduction, Genes, Insect, Homeodomain Proteins, Gene Expression Regulation, Developmental, Computational Biology, 3' Untranslated Regions, MicroRNAs

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