Cellular Trafficking of RNA Binding Protein, hnRNP A1 after ethanol (EtOH) & acetate exposure in neuronal cells

Alcohol binge-drinking is a behavior with wide-ranging implications for neuronal health and neurodegenerative diseases. One observed consequence of binge- drinking is altered microRNA expression, which can be mediated by RNA-binding proteins (RBPs). RBPs play a critical role in regulating RNA metabolism, including splicing, stabilization, and transport. Previously, the Pak Lab have shown RBPs regulate microRNA biogenesis, such as that of miR-9, which is highly enriched in the central nervous system and is critical for neuronal development. Among these, hnRNP A1 is a key RNA- binding protein involved in regulating microRNA binding to their target mRNAs or control their degradation, influencing various cellular processes. Dysfunction of hnRNPA1 has been linked to neurodegenerative diseases, such as Alzheimer's and Huntington's disease, though the precise mechanisms remain unclear. Previous animal studies revealed hnRNP A1 remain in the nucleus across different brain regions in both male and female rats. Conversely, in neuronal cells, hnRNP A1 translocated from the nucleus to the cytoplasm upon alcohol treatment, which contradicted the findings in the animal model. We hypothesized the potential in vivo and in vitro discrepancy could be explained by the effects of EtOH’s metabolite, acetate, in the brain rather than EtOH. We treated neuronal cells with varying concentrations of acetate at different time points to examine its effect on hnRNP A1 localization. We hypothesized that acetate would not alter hnRNP A1 localization