RNA and protein composition of pathogenic RNP granules Evan T. Lester1,2, Joshua R. Wheeler1,2, Roy Parker1,3, 1University of Colorado, Boulder, CO, USA; 2University of Colorado School of Medicine, Aurora, CO, USA; 3HHMI
Stress granules are RNA and protein assemblies that form in the cytoplasm of cells during cellular stress. Components of stress granules appear to accumulate in neurodegenerative disease. Aggregation of the stress granule resident protein Fused in Sarcoma (FUS) is found in the muscle and neurons of ALS patients and is thought to be a key driver in disease progression. How the properties of stress granules and pathologic FUS granules relate remains unknown. Mutations in the nuclear localization signal of FUS are causative for ALS and result in the cytoplasmic aggregation of FUS in unstressed conditions. Through isolating these cytoplasmic FUS aggregates from cellular models, we are exploring how the protein and RNA composition of pathogenic granules relates to that of stress granules and how this composition changes during stress. Our work has identified a number similarities and differences between pathologic FUS granules and stress granules. Current experiments are underway to confirm these observations and test their functional implications in disease relevant systems. This work will hopefully help elucidate the link between stress granules and pathogenic RNP granules that are the hallmark of many neurodegenerative diseases.
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