MicroRNA targets in Drosophila

By Anton J. Enright, Bino John, Ulrike Gaul, Thomas Tuschl, Christopher Sander, Debora Marks. Genome Biology, 2003

3,033 citations recorded by the source corpus.

BackgroundThe 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.ResultsThese 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.ConclusionsThe 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1f47f4c161d8ce01c000e49232cfd3e3f2fcdd22

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Citations in the corpus

Perspective: machines for RNAi. (2005, background): “The first position of a small RNA in RISC does not to contribute to binding, as was first noted in studies designed to predict miRNA targets (Enright et al. 2003; Lewis et al. 2003; Stark et al. 2003).”
A guide through present computational approaches for the identification of mammalian microRNA targets (2006, background): “During 2003, several groups independently developed the first computational miRNA target prediction programs focused on the fruit fl”
MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. (2007, methodology): “We used Miranda (Enright et al., 2003; John et al., 2004) to scan for energetically favorable binding sites.”
Novel and Stress-Regulated MicroRNAs and Other Small RNAs from Arabidopsis (2004, background): “These small RNAs might target promoter regions of protein coding genes for transcriptional gene silencing (Park et al., 2002; Ambros et al., 2003b; Finnegan and Matzke, 2003; Bartel, 2004).”
Human MicroRNA Targets (2004, methodology): “In choosing these parameters, we drew on experience from careful analysis of target predictions in Drosophila (Enright et al. 2003) as well as proposed human targets of virus-encoded miRNAs (Pfeffer et al.”
MicroRNA: Biogenesis, Function and Role in Cancer (2010, background): “miRNA:mRNA interaction can still occur in the presence of a G:U wobble but it effects specificity and activity of miRNA [156, 157, 163].”
Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis (2005, background): “While several publications predict target genes for Drosophila and human miRNA (19,20), only a few have been confirmed using reporter genes.”
Principles of MicroRNA–Target Recognition (2005, background): “, below the average for random matches) and Brd was thus not predicted as a miR-4 target previously [26,28,35].”
Molecular mechanisms of translational control (2004, background): “So far, several hundred miRNAs have been described in plants and animals that regulate a broad spectrum of biological processes, which range from cell metabolism to cell differentiation, cell growth and apoptosi”
MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer (2015, background): “MiRanda Seed match, conservation, and free energy Score [60]”
A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. (2006, background): “One group of approaches (Enright et al., 2003; John et al., 2004; Kiriakidou et al., 2004) is based on variants of the dynamic programming solution to the ‘‘local sufﬁx alignment’’ problem (Gusﬁeld, 1997).”
Tools for Sequence-Based miRNA Target Prediction: What to Choose? (2016, methodology): “in 2003 and designed to find potential target sites for miRNAs in the genomic sequence [81].”
TarBase: A comprehensive database of experimentally supported animal microRNA targets. (2005, background): “A majority of these 14 programs similar to a set of experimentally supported miRNA targets (Enright et al. 2003; Stark et al. 2003; John et al. 2004; Kiriakidou et al. 2004; Rajewsky and Socci 2004).”