The University of Colorado-Denver has been awarded a $522,001 Project Grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846). The 5-year grant supports research to investigate the mechanistic underpinnings of how the transcription factor DUX4 induces aberrant RNA processing and loss of RNA quality control in facioscapulohumeral muscular dystrophy (FSHD). Using a combination of biochemistry, genome engineering, proteomics, and genomics, the researchers will determine the mechanisms by which DUX4 alters splicing and targets factors that degrade aberrant transcripts via the ubiquitin-proteasome system. Successful completion of this research could elucidate how DUX4 rewires the post-transcriptional gene regulatory network in muscle cells, which could aid in the discovery of novel FSHD therapies given the role of perturbed RNA metabolism in many muscle diseases.
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