Transcriptome profiling of aging Drosophila photoreceptors reveals gene expression trends that correlate with visual senescence

Abstract

BackgroundAging is associated with functional decline of neurons and increased incidence of both neurodegenerative and ocular disease. Photoreceptor neurons in Drosophila melanogaster provide a powerful model for studying the molecular changes involved in functional senescence of neurons since decreased visual behavior precedes retinal degeneration. Here, we sought to identify gene expression changes and the genomic features of differentially regulated genes in photoreceptors that contribute to visual senescence.ResultsTo identify gene expression changes that could lead to visual senescence, we characterized the aging transcriptome of Drosophila sensory neurons highly enriched for photoreceptors. We profiled the nuclear transcriptome of genetically-labeled photoreceptors over a 40 day time course and identified increased expression of genes involved in stress and DNA damage response, and decreased expression of genes required for neuronal function. We further show that combinations of promoter motifs robustly identify age-regulated genes, suggesting that transcription factors are important in driving expression changes in aging photoreceptors. However, long, highly expressed and heavily spliced genes are also more likely to be downregulated with age, indicating that other mechanisms could contribute to expression changes at these genes. Lastly, we identify that circular RNAs (circRNAs) strongly increase during aging in photoreceptors.ConclusionsOverall, we identified changes in gene expression in aging Drosophila photoreceptors that could account for visual senescence. Further, we show that genomic features predict these age-related changes, suggesting potential mechanisms that could be targeted to slow the rate of age-associated visual decline.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4304-3) contains supplementary material, which is available to authorized users.

Proper splicing contributes to visual function in the aging Drosophila eye

“…We then performed phototaxis assays using a T‐maze apparatus, in which flies were given a choice between light (positive phototaxis, preference index 1.0) and dark (negative phototaxis, preference index −1.0). We previously showed that male flies have a significant decrease in phototactic behavior between days 10 and 40, indicative of reduced visual function (Hall et al, 2017). Because both phototaxis and visual senescence differ between male and female flies, and because the original transcriptome profiling was performed in male flies, here we examined phototaxis in young male flies expressing RNAi against each candidate gene.…”

“…Previously, we showed that genes involved in splicing have altered expression in aging Drosophila photoreceptors (Hall et al, 2017). Here, we sought to determine whether decreased levels of individual splicing factors in aging photoreceptors could contribute to the decline in visual function with age.…”

“…Here, we sought to determine whether decreased levels of individual splicing factors in aging photoreceptors could contribute to the decline in visual function with age. To do this, we first identified genes that were significantly differentially expressed in photoreceptors between days 10 and 40 using DESeq2 (adjusted p ‐value < 0.005) and compared these with genes that had the Gene Ontology (GO) term “RNA splicing”; 93% of male flies survived until day 40 under our experimental conditions, with a maximal lifespan of 80–85 days (Hall et al, 2017). We identified 30 genes involved in RNA splicing that were differentially expressed between day 10 and 40 in photoreceptors (Figure 1a, Supporting Information Table S1).…”

“…As in other organisms and tissues, aging Drosophila photoreceptors show altered expression of many genes involved in RNA processing and splicing (Hall et al, 2017). We previously showed that the altered gene expression profile of aging photoreceptors correlates with a decline in visual behavior, termed visual senescence (Carbone et al, 2016; Hall et al, 2017).…”

“…We previously showed that the altered gene expression profile of aging photoreceptors correlates with a decline in visual behavior, termed visual senescence (Carbone et al, 2016; Hall et al, 2017). As other transcriptome studies have also shown a correlation between splicing factor expression and splicing during aging (Stegeman & Weake, 2017), we wondered whether age‐associated alterations in splicing could contribute to visual senescence in flies.…”