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      Eye Development under the control of SRp55/B52-Mediated Alternative Splicing of eyeless

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      PLoS ONE
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          Abstract

          The genetic programs specifying eye development are highly conserved during evolution and involve the vertebrate Pax-6 gene and its Drosophila melanogaster homolog eyeless ( ey). Here we report that the SR protein B52/SRp55 controls a novel developmentally regulated splicing event of eyeless that is crucial for eye growth and specification in Drosophila. B52/SRp55 generates two isoforms of eyeless differing by an alternative exon encoding a 60-amino-acid insert at the beginning of the paired domain. The long isoform has impaired ability to trigger formation of ectopic eyes and to bind efficiently Eyeless target DNA sequences in vitro. When over-produced in the eye imaginal disc, this isoform induces a small eye phenotype, whereas the isoform lacking the alternative exon triggers eye over-growth and strong disorganization. Our results suggest that B52/SRp55 splicing activity is used during normal eye development to control eye organogenesis and size through regulation of eyeless alternative splicing.

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          Most cited references54

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          Understanding alternative splicing: towards a cellular code.

          In violation of the 'one gene, one polypeptide' rule, alternative splicing allows individual genes to produce multiple protein isoforms - thereby playing a central part in generating complex proteomes. Alternative splicing also has a largely hidden function in quantitative gene control, by targeting RNAs for nonsense-mediated decay. Traditional gene-by-gene investigations of alternative splicing mechanisms are now being complemented by global approaches. These promise to reveal details of the nature and operation of cellular codes that are constituted by combinations of regulatory elements in pre-mRNA substrates and by cellular complements of splicing regulators, which together determine regulated splicing pathways.
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            Alternative splicing: new insights from global analyses.

            Recent analyses of sequence and microarray data have suggested that alternative splicing plays a major role in the generation of proteomic and functional diversity in metazoan organisms. Efforts are now being directed at establishing the full repertoire of functionally relevant transcript variants generated by alternative splicing, the specific roles of such variants in normal and disease physiology, and how alternative splicing is coordinated on a global level to achieve cell- and tissue-specific functions. Recent progress in these areas is summarized in this review.
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              Alternative splicing: increasing diversity in the proteomic world.

              How can the genome of Drosophila melanogaster contain fewer genes than the undoubtedly simpler organism Caenorhabditis elegans? The answer must lie within their proteomes. It is becoming clear that alternative splicing has an extremely important role in expanding protein diversity and might therefore partially underlie the apparent discrepancy between gene number and organismal complexity. Alternative splicing can generate more transcripts from a single gene than the number of genes in an entire genome. However, for the vast majority of alternative splicing events, the functional significance is unknown. Developing a full catalog of alternatively spliced transcripts and determining each of their functions will be a major challenge of the upcoming proteomic era.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS ONE
                plos
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2007
                28 February 2007
                : 2
                : 2
                : e253
                Affiliations
                [1]Institut de Génétique Moléculaire de Montpellier (IGMM), UMR 5535, Université de Montpellier II, Centre National de Recherche Scientifique (CNRS), Montpellier, France
                Centre de Regulació Genòmica, Spain
                Author notes
                * To whom correspondence should be addressed. E-mail: jamal.tazi@ 123456igmm.cnrs.fr

                Conceived and designed the experiments: JT WF FJ JS. Performed the experiments: WF FJ. Analyzed the data: JT WF FJ. Contributed reagents/materials/analysis tools: FJ JS. Wrote the paper: JT.

                Article
                07-PONE-RA-00670
                10.1371/journal.pone.0000253
                1803029
                17327915
                322d632d-327b-4876-8357-08edc75c8bb9
                Fic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 25 January 2007
                : 31 January 2007
                Page count
                Pages: 10
                Categories
                Research Article
                Molecular Biology
                Genetics and Genomics/Animal Genetics
                Genetics and Genomics/Gene Expression
                Molecular Biology/RNA Splicing
                Genetics and Genomics/Animal Genetics
                Genetics and Genomics/Gene Expression
                Molecular Biology
                Molecular Biology/RNA Splicing

                Uncategorized
                Uncategorized

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