Profiling tissue-specific modulation of gene expression in response to insulin signalling in Drosophila
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ABSTRACT:
PROVIDER: PRJNA503894 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8159610.fastq.gz | Fastqsanger.gz | |||
| SRR8159620.fastq.gz | Fastqsanger.gz | |||
| SRR8159630.fastq.gz | Fastqsanger.gz | |||
| SRR8159640.fastq.gz | Fastqsanger.gz | |||
| SRR8159650.fastq.gz | Fastqsanger.gz |
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2021-03-20 | GSE151826 | GEO
Project description:We investigated tissue-specific regulation of gene expression in a long lived Drosophila IIS mutant (dilp2-3,5) compared to its control (wDah). As in the majority of Drosophila laboratory strains, the endosymbiont Wolbachia was present; in the absence of Wolbachia, life extension through dilp2-3,5 is abrogated (Grönke et al. 2010). To control for this, we additionally included strains of the same genotypes that lacked Wolbachia (dilp2-3,5T, wDahT). We quantified gene expression concurrently on the level of the proteome and the transcriptome, in four key tissues: brain, gut, fat body, and muscle. Proteome quantification was carried out on five biological replicates per experimental group. Corresponding transcriptome quantification was carried out on three biological replicates per experimental group, and published on GEO (accession number *GSE122190*)
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Project description:Background: Despite the prevalence and biological relevance of both signalling pathways and alternative pre-mRNA splicing, our knowledge of how intracellular signalling impacts on alternative splicing regulation remains fragmentary. We report a genome-wide analysis of changes in alternative splicing using splicing-sensitive microarrays, induced by activation of two distinct signalling 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 posttranscriptional 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 with carbohydrate metabolism and cellular signalling are enriched among genes regulated by insulin and wingless, respectively. Computational searches identify pathway-specific sequence motifs enriched near regulated 5â splice sites. Conclusion: Taken together, our data indicate that signalling 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 cross-talk between different signalling pathways. To monitor transcriptional and alternative splicing changes induced by activation of the insulin and wingless pathways, a custom-designed microarray platform was employed featuring probes for all Drosophila genes for which different mRNA isoforms generated by alternative splicing have been described (see Blanchette M, Green RE, Brenner SE, Rio DC: Global analysis of positive and negative pre-mRNA splicing regulators in Drosophila. Genes Dev 2005, 19(11):1306-1314.). Three biological replicates of total RNA isolated after pathway activation or controls (untreated cells for insulin, control dsRNA for wingless) were purified, reverse transcribed into cDNA and labelled with Cy5 or Cy3 fluorochromes and the cDNA was hybridized to the microarray,
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Project description:Enhanced insulin signalling ameliorates C9orf72 hexanucleotide repeat expansion toxicity in Drosophila
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Project description:We investigated tissue-specific regulation of gene expression in a long lived Drosophila IIS mutant (dilp2-3,5) compared to its control (wDah). The longevity of dilp2-3,5 mutants only occurs in the presence of the endosymbiotic bacteria Wolbachia. We therefore use flies (10 day old) in the presence (wDah and dilp2-3,5) or absence (wDahT and dilp2-3,5T) of Wolbachia to identify the changes in gene expression that could potentially be causal for longevity. We quantified gene expression for all experimental groups, concurrently on the level of the proteome and the transcriptome and in four key tissues: brain, gut, fat body, and muscle. Transcriptome quantification was carried out on three biological replicates per experimental group. Corresponding proteome quantification was carried out on five biological replicates per experimental group, and published on PRIDE (accession number PXD011589).
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Project description:We previously found that the Drosophila FoxA transcription Fork Head (FKH) is necessary for reduced insulin signalling to extend lifespan. We have now identified that increased expression of FKH in neurons alone is sufficient to extend healthy lifespan. We carried out RNA-sequencing in head tissue on controls (daGS>InRDN,GFP-RNAi without RU-486) and reduced insulin signalling with control RNAi (daGS>InRDN,GFP-RNAi with RU486) and reduced insulin signalling with FKH RNAi (daGS>InRDN,FKH-RNAi with RU486). InR-DN stock used: K1409A.
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Project description:Background: Despite the prevalence and biological relevance of both signalling pathways and alternative pre-mRNA splicing, our knowledge of how intracellular signalling impacts on alternative splicing regulation remains fragmentary. We report a genome-wide analysis of changes in alternative splicing using splicing-sensitive microarrays, induced by activation of two distinct signalling 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 posttranscriptional 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 with carbohydrate metabolism and cellular signalling are enriched among genes regulated by insulin and wingless, respectively. Computational searches identify pathway-specific sequence motifs enriched near regulated 5’ splice sites. Conclusion: Taken together, our data indicate that signalling 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 cross-talk between different signalling pathways.
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