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Spinal muscle atrophy (SMA) is an autosomal recessive neurodegenerative disease which is characterized by the loss of α motor neurons resulting in progressive muscle atrophy. Reduced amount of functional survival motor neuron (SMN) protein due to mutations or deletion in theSMN1gene is the cause of SMA. A potential treatment strategy for SMA is to upregulate levels of SMN protein originating from theSMN2gene compensating in part for the absence of functionalSMN1gene. Although there exists a sizeable literature onSMN2inducing compounds, there is comparatively less known about the signaling pathways which modulate SMN levels. Here, we report a significant induction in SMN mRNA and protein following p38 activation by Anisomycin. We demonstrate that Anisomycin activation of p38 causes a rapid cytoplasmic accumulation of HuR, a RNA binding protein which binds to and stabilizes the AU-rich element within the SMN transcript. The stabilization of SMN mRNA, rather than transcriptional induction results in an increase in SMN protein. Our demonstration of SMN protein regulation through the p38 pathway and the role of HuR in this modulation may help in the identification and characterization of p38 pathway activators as potential therapeutic compounds for the treatment of SMA.

p38 Mitogen-activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR