Dataset Information

Non-EST-based prediction of novel alternatively spliced cassette exons with cell signaling function in Caenorhabditis elegans and human.

ABSTRACT: To better understand the complex role that alternative splicing plays in intracellular signaling, it is important to catalog the numerous splice variants involved in signal transduction. Therefore, we developed PASE (Prediction of Alternative Signaling Exons), a computational tool to identify novel alternative cassette exons that code for kinase phosphorylation or signaling protein-binding sites. We first applied PASE to the Caenorhabditis elegans genome. In this organism, our algorithm had an overall specificity of > or =76.4%, including 33 novel cassette exons that we experimentally verified. We then used PASE to analyze the human genome and made 804 predictions, of which 308 were found as alternative exons in the transcript database. We experimentally tested 384 of the remaining unobserved predictions and discovered 26 novel human exons for a total specificity of > or =41.5% in human. By using a test set of known alternatively spliced signaling exons, we determined that the sensitivity of PASE is approximately 70%. GO term analysis revealed that our exon predictions were found in the introns of known signal transduction genes more often than expected by chance, indicating PASE enriches for splice variants that function in signaling pathways. Overall, PASE was able to uncover 59 novel alternative cassette exons in C. elegans and humans through a genome-wide ab initio prediction method that enriches for exons involved in signaling.

SUBMITTER: Leparc GG

PROVIDER: S-EPMC1904267 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Non-EST-based prediction of novel alternatively spliced cassette exons with cell signaling function in Caenorhabditis elegans and human.

Leparc German Gaston GG Mitra Robi David RD

Nucleic acids research 20070422 10

To better understand the complex role that alternative splicing plays in intracellular signaling, it is important to catalog the numerous splice variants involved in signal transduction. Therefore, we developed PASE (Prediction of Alternative Signaling Exons), a computational tool to identify novel alternative cassette exons that code for kinase phosphorylation or signaling protein-binding sites. We first applied PASE to the Caenorhabditis elegans genome. In this organism, our algorithm had an o ...[more]

PMID: 17452356

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Project description:The Dscam gene in the fruit fly, Drosophila melanogaster, contains twenty-four exons, four of which are composed of tandem arrays that each undergo mutually exclusive alternative splicing (4, 6, 9 and 17), potentially generating 38,016 protein isoforms. This degree of transcript diversity has not been found in mammalian homologs of Dscam. We examined the molecular evolution of exons within this gene family to locate the point of divergence for this alternative splicing pattern.Using the fruit fly Dscam exons 4, 6, 9 and 17 as seed sequences, we iteratively searched sixteen genomes for homologs, and then performed phylogenetic analyses of the resulting sequences to examine their evolutionary history. We found homologs in the nematode, arthropod and vertebrate genomes, including homologs in several vertebrates where Dscam had not been previously annotated. Among these, only the arthropods contain homologs arranged in tandem arrays indicative of mutually exclusive splicing. We found no homologs to these exons within the Arabidopsis, yeast, tunicate or sea urchin genomes but homologs to several constitutive exons from fly Dscam were present within tunicate and sea urchin. Comparing the rate of turnover within the tandem arrays of the insect taxa (fruit fly, mosquito and honeybee), we found the variants within exons 4 and 17 are well conserved in number and spatial arrangement despite 248-283 million years of divergence. In contrast, the variants within exons 6 and 9 have undergone considerable turnover since these taxa diverged, as indicated by deeply branching taxon-specific lineages.Our results suggest that at least one Dscam exon array may be an ancient duplication that predates the divergence of deuterostomes from protostomes but that there is no evidence for the presence of arrays in the common ancestor of vertebrates. The different patterns of conservation and turnover among the Dscam exon arrays provide a striking example of how a gene can evolve in a modular fashion rather than as a single unit.

Dataset Information

Non-EST-based prediction of novel alternatively spliced cassette exons with cell signaling function in Caenorhabditis elegans and human.

Publications

Non-EST-based prediction of novel alternatively spliced cassette exons with cell signaling function in Caenorhabditis elegans and human.

Similar Datasets

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