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      MicroRNA Targets in Drosophila


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          We present a novel three-step method for whole-genome prediction of miRNA target genes, validated using known examples. We apply the method to discover hundreds of potential target genes in D. melanogaster.


          The recent discoveries of microRNAs (miRNAs) and characterization of the first few targets of their gene products in Caenorhabditis elegans and Drosophila melanogaster have set the stage for elucidation of a novel network of regulatory control. Here, we present a novel three-step method for whole-genome prediction of miRNA target genes, validated using known examples. We apply the method to discover hundreds of potential target genes in D. melanogaster. For each miRNA, target genes are selected based on (a) pattern of sequence complementarity using a position-weighted local alignment algorithm, (b) energy calculation of RNA-RNA duplex formation, and (c) conservation of target sites in related genomes. Application to the D. melanogaster, D pseudoobscura and Anopheles gambiae genomes in this manner, identifies several hundred target genes potentially regulated by one or more known miRNAs.

          These potential targets are enriched for genes that are expressed at specific developmental stages and are involved in cell fate specification, morphogenesis and the coordination of developmental processes, as well as the function of the nervous system in the mature organism. High-ranking targets are two-fold enriched in transcription factors and include genes already known to be under translational regulation. Our results reaffirm the thesis that miRNAs play an important role in establishing the complex spatial and temporal patterns of gene activity necessary for the orderly progression of development and point to additional roles in the function of the mature organism.

          The emerging combinatorics of miRNA target sites in the 3' UTRs 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 regulated target. Typically, more than one miRNA regulates one message, indicative of cooperative control of translation. Conversely, one miRNAs may have several targets, reflecting target multiplicity.

          As a guide to targeted experiments, we provide detailed online information [1] about target genes and binding sites for each miRNA and about miRNAs for each gene, ranked by likelihood of match. The target prediction tool can be applied to any similar pair of genomes with identified miRNA sequences.

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          Most cited references62

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            Identification of common molecular subsequences.

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              Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.

              During C. elegans development, the temporal pattern of many cell lineages is specified by graded activity of the heterochronic gene Lin-14. Here we demonstrate that a temporal gradient in Lin-14 protein is generated posttranscriptionally by multiple elements in the lin-14 3'UTR that are regulated by the heterochronic gene Lin-4. The lin-14 3'UTR is both necessary and sufficient to confer lin-4-mediated posttranscriptional temporal regulation. The function of the lin-14 3'UTR is conserved between C. elegans and C. briggsae. Among the conserved sequences are seven elements that are each complementary to the lin-4 RNAs. A reporter gene bearing three of these elements shows partial temporal gradient activity. These data suggest a molecular mechanism for Lin-14p temporal gradient formation: the lin-4 RNAs base pair to sites in the lin-14 3'UTR to form multiple RNA duplexes that down-regulate lin-14 translation.

                Author and article information

                Genome Biol
                Genome Biol
                Genome Biology
                BioMed Central
                14 October 2003
                : 4
                : 11
                : P8
                [1 ]Computational Biology Center, Memorial Sloane Kettering Cancer Center, 1275 York Avenue. New York, NY 10021, USA
                [2 ]Developmental Neurogenetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
                [3 ]RNA Molecular Biology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
                [4 ]Columbia Genome Center, Columbia University, Russ Berrie Pavilion, 1150 St. Nicholas Avenue, New York, NY 10032, USA
                Copyright © 2003 BioMed Central Ltd
                : 13 October 2003
                Deposited Research Article



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