Differential activity of EWG transcription factor isoforms identifies a subset of differentially regulated genes important for synaptic growth regulation.
The vast majority of genes in the human genome is alternatively spliced. The functional consequences of this type of post-transcriptional gene regulation that is particularly prominent in the brain, however, remains largely elusive. Here we analyzed the role of alternative splicing in the transcription factor erect wing (ewg) in Drosophila and dissect its function through differential rescue with transgenes encoding different isoforms. Transgenes expressing the SC3 ORF isoform fully rescue viability and synaptic growth defects. In contrast, transgenes expressing the ∆DJ isoform, that lack exons D and J, have a lower activity as inferred from their expression levels and exert reduced rescue of viability and synaptic growth defects. By comparison of the gene expression profile of ewg(l1) mutants rescued either by the SC3 ORF or the ∆DJ transgene, we identified a set of genes whose expression is exclusively restored by the SC3 isoform. These genes are mostly involved in regulating gene expression while a core function of EWG is indicated by the regulation of metabolic genes by both isoforms. In conclusion, we demonstrated that differential rescue with different isoform encoding transgenes of the transcription factor EWG identifies a unique set of genes associated with synaptic growth regulation.
Haussmann
Irmgard U
IU
School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Soller
Matthias
M
D017398:Alternative Splicing; D000818:Animals; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009469:Neuromuscular Junction / Q000254:growth & development* / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D040081:Protein Array Analysis; D020033:Protein Isoforms / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D029721:Drosophila Proteins; C081334:EWG protein, Drosophila; D009479:Neuropeptides; D020033:Protein Isoforms; D014157:Transcription Factors