Ethanol induces subcellular trafficking of the RNA-binding protein, hnRNP A1, in neuronal cells <i>in vitro</i>, but not in the peripubertal rat brain

The RNA-binding protein, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), plays a critical role in RNA metabolism, including splicing, stabilization, and transport. hnRNP A1 predominantly resides in the cell nucleus; however, it can be dynamically trafficked to the cytoplasm in response to cellular stressors, such as osmotic or oxidative stress. Although the cytoplasmic functions of hnRNP A1 are not well understood, our previous work demonstrated that hnRNP A1 associates with mature microRNAs in the cytoplasm, including those that are regulated by adolescent binge-pattern alcohol use. Therefore, this study tested the effects of repeated binge-pattern ethanol (EtOH) exposure during adolescence on hnRNP A1 subcellular localization in the rat brain and in neuronal-derived cell lines. Our results showed that EtOH exposure induced hnRNP A1 re-localization from the nucleus to the cytoplasm in neuronal cell lines, but not in the rat brain. Moreover, the primary end metabolite of EtOH, acetate, failed to induce hnRNP A1 re-localization in neuronal cell lines, suggesting that EtOH metabolism in vivo abrogated hnRNP A1 subcellular trafficking. We also observed that EtOH-induced hnRNP A1 re-localization to the cytoplasm was correlated with increased neuronal cell volume, suggesting that osmotic stress could be a cellular stressor driving subcellular trafficking in neurons. Notably, our study also revealed that there are brain region- and sex-specific differences in hnRNP A1 expression levels in the adolescent rat brain.