Dg-Dys-Syn1 signaling in Drosophila regulates stress related miRNA profile. Evgeniia V Edeleva, April K Marrone, Halyna R Shcherbata. MPRG of Gene Expression and Signaling, Max Planck Institute, Goettingen, Germany.
Muscular dystrophies (MDs) are fatal inherited neuromuscular disorders associated with deficiencies in the dystrophin-glycoprotein complex (DGC). Components of the DGC are evolutionary conserved from flies to humans making Drosophila melanogaster a good model for better understanding of DGC function and identifying novel mechanisms of its action. Using D. melanogaster as a model we previously found that stresses accelerate the onset of MDs and can even induce severe muscle degeneration symptoms in wt animals. miRNAs are good candidates to act as stress response factors as they allow for a quick cellular response with no transcriptional reorganization and synthesis of new cellular proteins. We analyzed miRNA profiles in dystrophic and wt animals under normal conditions and stress imposed by high temperature. After careful analysis of microarray data we grouped analyzed miRNAs into those linked to dystrophy and/or stress. Stress related miRNAs are of particular importance as they show that the DGC has a more general role in cellular homeostasis regulation compromised under stress. The DGC serves as a scaffold for multiple proteins, including Syn and nNOS. It was already shown in vertebrates that a pathway involving Dys-Syn-nNOS signaling regulates histone modifications modulating transcription of multiple genes (including miRNAs) in response to different conditions. We further showed that similar pathway involving Dg-Dys-Syn1 signaling exists also in flies suggesting that Dg-Dys-Syn1 via specific HDACs regulates expression of miRNAs implemented in stress response.