Dysfunctional RNA binding proteins and stress granules in multiple sclerosis

Abstract Dysfunction of the RNA binding protein (RBP) heterogeneous nuclear ribonuclear protein A1 (hnRNP A1) has been shown to contribute to the pathogenesis of neurodegenerative diseases, but its involvement in multiple sclerosis (MS) is largely unknown. In a neuronal cell line, interferon-γ caused hnRNP A1 nucleocytoplasmic mislocalization; colocalization of hnRNP A1 in stress granules (SGs); and inhibition of translation. Neurons in the brain of a MS patient showed pathogenic RBP dysfunction, including nuclear depletion of hnRNP A1, its mislocalization to the cytoplasm, and its colocalization in SGs. These data indicate a role for dysfunctional hnRNP A1 in the pathogenesis of MS.