Bulk RNA-seq of Drosophila melanogaster expressing C9orf72 and the associated dipeptide repeat proteins (poly-GA36, poly-GR36, and poly-PR36)
Intronic hexanucleotide repeat expansions in the C9orf72 gene are the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). These intronic hexanucleotide repeat expansions result in the production of toxic dipeptide repeat proteins (DPRs), which contribute to neurodegeneration. Our lab previously created fruit fly models expressing 36(G4C2) repeats and individual DPR proteins. This study investigates the transcriptomic effects of C9orf72-associated DPRs in Drosophila melanogaster. Bulk RNA sequencing (RNA-seq) was performed on adult fly heads to assess gene expression changes across three experimental dimensions: 1. Disease progression: We analysed the effect of C9orf72 expressing flies using the elavGS pan-neuronal driver at three time points (days 3, 6, and 9) representing early, mid, and late stages of disease progression.  2. Dipeptide repeat proteins comparison: We compared the transcriptomic profiles of flies expressing different dipeptide repeat proteins (poly-GA36, poly-GR36, and poly-PR36) using the nSybGS driver. 3. Driver effects on gene expression: We evaluated the differences between the two pan-neuronal drivers, elavGS and nSybGS, on gene expression.
Intronic hexanucleotide repeat expansions in the C9orf72 gene are the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). These intronic hexanucleotide repeat expansions result in the production of toxic dipeptide repeat proteins (DPRs), which contribute to neurodegeneration. Our lab previously created fruit fly models expressing 36(G4C2) repeats and individual DPR proteins. This study investigates the transcriptomic effects of C9orf72-associated DPRs in Drosophila melanogaster. Bulk RNA sequencing (RNA-seq) was performed on adult fly heads to assess gene expression changes across three experimental dimensions: 1. Disease progression: We analysed the effect of C9orf72 expressing flies using the elavGS pan-neuronal driver at three time points (days 3, 6, and 9) representing early, mid, and late stages of disease progression.  2. Dipeptide repeat proteins comparison: We compared the transcriptomic profiles of flies expressing different dipeptide repeat proteins (poly-GA36, poly-GR36, and poly-PR36) using the nSybGS driver. 3. Driver effects on gene expression: We evaluated the differences between the two pan-neuronal drivers, elavGS and nSybGS, on gene expression.
European Bioinformatics Institute