A genome-wide analysis of the response to insulin and wingless activation using splicing-sensitive microarrays shows distinct but overlapping programs of transcriptional and posttranscriptional regulation

Blanchette, Marco

Boue, Stephanie

Castelo, Robert

Hartmann, Britta

Rio, Donald C

Valcárcel, Juan

English

PubMed

BackgroundDespite the prevalence and biological relevance of both signaling pathways and alternative pre-mRNA splicing, our knowledge of how intracellular signaling impacts on alternative splicing regulation remains fragmentary. We report a genome-wide analysis using splicing-sensitive microarrays of changes in alternative splicing induced by activation of two distinct signaling pathways, insulin and wingless, in Drosophila cells in culture.ResultsAlternative splicing changes induced by insulin affect more than 150 genes and more than 50 genes are regulated by wingless activation. About 40% of the genes showing changes in alternative splicing also show regulation of mRNA levels, suggesting distinct but also significantly overlapping programs of transcriptional and post-transcriptional regulation. Distinct functional sets of genes are regulated by each pathway and, remarkably, a significant overlap is observed between functional categories of genes regulated transcriptionally and at the level of alternative splicing. Functions related to carbohydrate metabolism and cellular signaling are enriched among genes regulated by insulin and wingless, respectively. Computational searches identify pathway-specific sequence motifs enriched near regulated 5' splice sites.ConclusionsTaken together, our data indicate that signaling cascades trigger pathway-specific and biologically coherent regulatory programs of alternative splicing regulation. They also reveal that alternative splicing can provide a novel molecular mechanism for crosstalk between different signaling pathways

eScholarship - University of California

Global analysis of alternative splicing regulation by insulin and wingless signaling in Drosophilacells

Britta Hartmann

Robert Castelo

Marco Blanchette

Stephanie Boue

Donald C Rio

Juan Valcárcel

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Global analysis of alternative splicing regulation by insulin and wingless signaling in Drosophila cells

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Global analysis of alternative splicing regulation by insulin and wingless signaling in cells

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Global analysis of alternative splicing regulation by insulin and wingless signaling in Drosophila cells

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