HuD regulates apoptosis in N2a cells by regulating Msi2 expression

by Naina Gaikwad, Rucha Sarwade, Sourav Halder, Gaurav Agarwal, Vasudevan Seshadri

HuD plays a critical role in neurite outgrowth, neuronal plasticity, and survival. However, HuD autoantibodies from patients with paraneoplastic gut dysmotility can trigger the apoptotic cascade in human neuroblastoma cell line and myenteric neurons. The mechanism by which HuD regulates the apoptotic pathway is unclear. Apoptosis is one of the underlying causes of neurodegenerative diseases like Alzheimer’s disease. In the current study, we found that HuD interacts with Msi2 transcript and positively regulates it in the mouse neuroblastoma (N2a) cells. MSI2 being an RNA binding protein has diverse mRNA targets and regulates the mitochondrial apoptotic pathway by interacting with and repressing APAF1 transcript. Conversely, the reduced levels of HuD leads to decreased Msi2 expression and increased APAF1 levels, which results in apoptosis in N2a cells. Overall, our research indicates that HuD and Msi2 possess an anti-apoptotic role in N2A cells.