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


RESULTS
Alternative 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.


CONCLUSIONS
Taken 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.
Hartmann
Britta
B
Centre de Regulació Genòmica, Parc de Recerca Biomèdica de Barcelona, Dr Aiguader 88, Barcelona, Spain. britta.hartmann@crg.es
Castelo
Robert
R
Blanchette
Marco
M
Boue
Stephanie
S
Rio
Donald C
DC
Valcárcel
Juan
J
D017398:Alternative Splicing; D000818:Animals; D050260:Carbohydrate Metabolism / Q000235:genetics; D002460:Cell Line; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D017344:Genes, Insect; D023281:Genomics; D007328:Insulin / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020239:Receptor Cross-Talk; D015398:Signal Transduction / Q000235:genetics*; D014158:Transcription, Genetic; D051155:Wnt1 Protein / Q000378:metabolism*
D029721:Drosophila Proteins; D007328:Insulin; D051155:Wnt1 Protein; C074622:wg protein, Drosophila