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

Britta Hartmann,Marco Blanchette,Donald C Rio,Robert Castelo,Stephanie Boue,Juan Valcárcel

doi:10.1186/gb-2009-10-1-r11

Abstract

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.

Highlights

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
Transcriptional changes induced upon activation of the insulin and wingless pathways in S2 cells Binding of insulin-like peptides to the insulin receptor in Drosophila cells leads to the activation of dPI3 kinase, which
Two significant motifs were identified, a uridine-rich motif associated with junctions regulated by insulin and an adenosine-rich motif associated with junctions regulated by the wingless pathway. These motifs were significantly enriched compared with their distribution in sets of control regions of comparable size derived from either constitutive or non-constitutive junctions that did not show differential regulation by the wingless or insulin pathways [63]. We propose that these motifs are part of the cis-acting elements through which signaling pathways regulate alternative pre-mRNA splicing

Summary

Introduction

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. Signaling pathways present a major mechanism by which cells communicate during development and as part of the normal physiology of organisms. The major signaling pathways have been shown to be remarkably conserved in their components and general biological role from insects and worms to mammals [1,2,3]. To exert their diverse functions, these pathways are used reiteratively, mainly by regulating different transcriptional programs depending on the cellular context. Positive- and negative-acting cisregulatory sequences influencing transcription have been characterized in the promoters of target genes, with targets of the same pathway sharing similar sequence motifs (reviewed in [4,5,6,7,8])

Methods

Results

Conclusion