Interferon-stimulated gene GBP1 protects SMN2 from degradation

Abstract

Abstract Spinal muscular atrophy (SMA) is lethal autosomal recessive disease of muscle due to the pathogenic variations of the survival motor neuron 1 (SMN) encoding the motor neuron (SMN1, MIM#600354). The mutations of SMN result in insufficient full-length of SMN protein, which leads to muscle atrophy and even respiratory involvement. No effective treatments are currently available. The SMN2 gene is a regulator of the phenotype and its copy number is associated with the severity of disease. Previous studies have demonstrated that the interferons and IRF-1 induce the expression of SMN. In the current study, we found that patients with more copies of SMN2 had higher levels of GBP1 in peripheral blood and the stability of SMN2 protein was better with the presence of guanylate-binding protein 1(GBP1). Therefore, the IFN-γ-induced GBP1 protects SMN2 from degradation. Our findings provided new insights into the treatment of SMA.