{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:15:29Z","timestamp":1754144129217,"version":"3.41.2"},"reference-count":37,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"crossref","award":["R01AA021517"],"award-info":[{"award-number":["R01AA021517"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007657","name":"Loyola University Chicago Stritch School of Medicine","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007657","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>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.<\/jats:p>","DOI":"10.1242\/bio.062010","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T16:21:18Z","timestamp":1750782078000},"source":"Crossref","is-referenced-by-count":1,"title":["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"],"prefix":"10.1242","volume":"14","author":[{"given":"Angela H. S.","family":"Fan","sequence":"first","affiliation":[{"name":"Loyola University Chicago Stritch School of Medicine , Department of Cell and Molecular Physiology, Maywood, IL 60153 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoldas","family":"Yildiz","sequence":"additional","affiliation":[{"name":"Loyola University Chicago Stritch School of Medicine , Department of Cell and Molecular Physiology, Maywood, IL 60153 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda A.","family":"Hartoun","sequence":"additional","affiliation":[{"name":"Loyola University Chicago Stritch School of Medicine , Department of Cell and Molecular Physiology, Maywood, IL 60153 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikayla L.","family":"Newby","sequence":"additional","affiliation":[{"name":"Loyola University Chicago Stritch School of Medicine , Department of Cell and Molecular Physiology, Maywood, IL 60153 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rujuta","family":"Durwas","sequence":"additional","affiliation":[{"name":"Loyola University Chicago Stritch School of Medicine , Department of Cell and Molecular Physiology, Maywood, IL 60153 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Ngai","sequence":"additional","affiliation":[{"name":"Loyola University Chicago Stritch School of Medicine , Department of Cell and Molecular Physiology, Maywood, IL 60153 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Flury","sequence":"additional","affiliation":[{"name":"Loyola University Chicago Stritch School of Medicine , Department of Cell and Molecular Physiology, Maywood, IL 60153 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-9754","authenticated-orcid":false,"given":"Toni R.","family":"Pak","sequence":"additional","affiliation":[{"name":"Loyola University Chicago Stritch School of Medicine , Department of Cell and Molecular Physiology, Maywood, IL 60153 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"2025071503483264600_BIO062010C1","doi-asserted-by":"publisher","first-page":"3605","DOI":"10.1073\/pnas.0409889102","article-title":"Regulation of heterogenous nuclear ribonucleoprotein A1 transport by phosphorylation in cells stressed by osmotic shock","volume":"102","author":"Allemand","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025071503483264600_BIO062010C2","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.alcohol.2016.10.010","article-title":"Adolescent binge-pattern alcohol exposure alters genome-wide DNA methylation patterns in the hypothalamus of alcohol-naive male offspring","volume":"60","author":"Asimes","year":"2017","journal-title":"Alcohol"},{"key":"2025071503483264600_BIO062010C3","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3390\/ncrna5010021","article-title":"microRNA expression profiles in the ventral hippocampus during pubertal development and the impact of peri-pubertal binge alcohol exposure","volume":"5","author":"Asimes","year":"2019","journal-title":"Noncoding RNA"},{"key":"2025071503483264600_BIO062010C4","doi-asserted-by":"publisher","first-page":"884197","DOI":"10.3389\/fnins.2022.884197","article-title":"Acute ethanol challenge differentially regulates expression of growth factors and miRNA expression profile of whole tissue of the dorsal hippocampus","volume":"16","author":"Barney","year":"2022","journal-title":"Front. Neurosci."},{"key":"2025071503483264600_BIO062010C5","doi-asserted-by":"publisher","first-page":"2596","DOI":"10.1210\/en.2018-00220","article-title":"Comparing Postnatal Development of Gonadal Hormones and Associated Social Behaviors in Rats, Mice, and Humans","volume":"159","author":"Bell","year":"2018","journal-title":"Endocrinology"},{"key":"2025071503483264600_BIO062010C6","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.biopha.2015.07.025","article-title":"Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight","volume":"74","author":"Bhat","year":"2015","journal-title":"Biomed. Pharmacother."},{"key":"2025071503483264600_BIO062010C7","doi-asserted-by":"publisher","first-page":"16793","DOI":"10.18632\/oncotarget.7589","article-title":"hnRNP A1-mediated translational regulation of the G quadruplex-containing RON receptor tyrosine kinase mRNA linked to tumor progression","volume":"7","author":"Cammas","year":"2016","journal-title":"Oncotarget"},{"key":"2025071503483264600_BIO062010C8","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.cld.2012.08.002","article-title":"Alcohol metabolism","volume":"16","author":"Cederbaum","year":"2012","journal-title":"Clin. Liver Dis."},{"key":"2025071503483264600_BIO062010C9","doi-asserted-by":"publisher","first-page":"659610","DOI":"10.3389\/fmolb.2021.659610","article-title":"A comprehensive analysis of the role of hnRNP A1 function and dysfunction in the pathogenesis of neurodegenerative disease","volume":"8","author":"Clarke","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"2025071503483264600_BIO062010C10","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1124\/pr.115.012138","article-title":"Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior","volume":"68","author":"Crews","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"2025071503483264600_BIO062010C11","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/s41422-019-0141-z","article-title":"PARylation regulates stress granule dynamics, phase separation, and neurotoxicity of disease-related RNA-binding proteins","volume":"29","author":"Duan","year":"2019","journal-title":"Cell Res."},{"key":"2025071503483264600_BIO062010C12","first-page":"8","article-title":"Individual susceptibility and alcohol effects: biochemical and genetic aspects","volume":"42","author":"Gemma","year":"2006","journal-title":"Ann. Ist. Super Sanita"},{"key":"2025071503483264600_BIO062010C13","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/s0736-5748(00)00017-4","article-title":"Neuroprotective effects of estrogens: potential mechanisms of action","volume":"18","author":"Green","year":"2000","journal-title":"Int. J. Dev. Neurosci."},{"key":"2025071503483264600_BIO062010C14","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nsmb1250","article-title":"The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a","volume":"14","author":"Guil","year":"2007","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2025071503483264600_BIO062010C15","doi-asserted-by":"publisher","first-page":"5744","DOI":"10.1128\/MCB.00224-06","article-title":"hnRNP A1 relocalization to the stress granules reflects a role in the stress response","volume":"26","author":"Guil","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"2025071503483264600_BIO062010C16","doi-asserted-by":"publisher","first-page":"1543809","DOI":"10.1155\/2016\/1543809","article-title":"Lipids and oxidative stress associated with ethanol-induced neurological damage","volume":"2016","author":"Hernandez","year":"2016","journal-title":"Oxid Med. Cell Longev."},{"key":"2025071503483264600_BIO062010C17","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.celrep.2018.06.094","article-title":"Hypertonic stress causes cytoplasmic translocation of neuronal, but not astrocytic, FUS due to impaired transportin function","volume":"24","author":"Hock","year":"2018","journal-title":"Cell Rep."},{"key":"2025071503483264600_BIO062010C18","doi-asserted-by":"publisher","first-page":"273","DOI":"10.2165\/00003088-198713050-00001","article-title":"Clinical pharmacokinetics of ethanol","volume":"13","author":"Holford","year":"1987","journal-title":"Clin. Pharmacokinet."},{"key":"2025071503483264600_BIO062010C19","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/S0929-6646(09)60374-0","article-title":"Alterations in oxidative stress status during early alcohol withdrawal in alcoholic patients","volume":"108","author":"Huang","year":"2009","journal-title":"J. Formos. Med. Assoc."},{"key":"2025071503483264600_BIO062010C20","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1210\/endo-103-1-212","article-title":"Developmental changes in testicular gonadotropin receptors: plasma gonadotropins and plasma testosterone in the rat","volume":"103","author":"Ketelslegers","year":"1978","journal-title":"Endocrinology"},{"key":"2025071503483264600_BIO062010C21","doi-asserted-by":"publisher","first-page":"ENEURO.0094-20.2020","DOI":"10.1523\/ENEURO.0094-20.2020","article-title":"Differential stability of miR-9-5p and miR-9-3p in the brain is determined by their unique Cis- and trans-acting elements","volume":"7","author":"Kim","year":"2020","journal-title":"eNeuro"},{"key":"2025071503483264600_BIO062010C22","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.neulet.2006.06.052","article-title":"Heme oxygenase protects hippocampal neurons from ethanol-induced neurotoxicity","volume":"405","author":"Ku","year":"2006","journal-title":"Neurosci. Lett."},{"key":"2025071503483264600_BIO062010C23","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.alcohol.2008.08.005","article-title":"Binge alcohol treatment of adolescent rats followed by alcohol abstinence is associated with site-specific differences in bone loss and incomplete recovery of bone mass and strength","volume":"42","author":"Lauing","year":"2008","journal-title":"Alcohol"},{"key":"2025071503483264600_BIO062010C24","doi-asserted-by":"publisher","first-page":"G452","DOI":"10.1152\/ajpgi.1994.267.3.G452","article-title":"Can the liver account for first-pass metabolism of ethanol in the rat?","volume":"267","author":"Levitt","year":"1994","journal-title":"Am. J. Physiol."},{"key":"2025071503483264600_BIO062010C25","doi-asserted-by":"publisher","first-page":"74","DOI":"10.3390\/ncrna9060074","article-title":"Age and 17beta-Estradiol (E(2)) facilitate nuclear export and argonaute loading of microRNAs in the female brain","volume":"9","author":"Linscott","year":"2023","journal-title":"Noncoding RNA"},{"key":"2025071503483264600_BIO062010C26","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2025071503483264600_BIO062010C27","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1002\/(SICI)1098-1063(2000)10:1&lt;122::AID-HIPO13&gt;3.0.CO;2-V","article-title":"Effects of acute and chronic ethanol exposure on spatial cognitive processing and hippocampal function in the rat","volume":"10","author":"Matthews","year":"2000","journal-title":"Hippocampus"},{"key":"2025071503483264600_BIO062010C28","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1111\/j.1530-0277.2008.00726.x","article-title":"Acute alcohol intake induces SOCS1 and SOCS3 and inhibits cytokine-induced STAT1 and STAT3 signaling in human monocytes","volume":"32","author":"Norkina","year":"2008","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"2025071503483264600_BIO062010C29","doi-asserted-by":"publisher","first-page":"e83166","DOI":"10.1371\/journal.pone.0083166","article-title":"Long-term effects of peripubertal binge EtOH exposure on hippocampal microRNA expression in the rat","volume":"9","author":"Prins","year":"2014","journal-title":"PLoS ONE"},{"key":"2025071503483264600_BIO062010C30","doi-asserted-by":"publisher","first-page":"E320","DOI":"10.1152\/ajpendo.00615.2009","article-title":"Binge-pattern alcohol exposure during puberty induces sexually dimorphic changes in genes regulating the HPA axis","volume":"298","author":"Przybycien-Szymanska","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"2025071503483264600_BIO062010C31","doi-asserted-by":"publisher","first-page":"e89320","DOI":"10.1371\/journal.pone.0089320","article-title":"Parental binge alcohol abuse alters F1 generation hypothalamic gene expression in the absence of direct fetal alcohol exposure","volume":"9","author":"Przybycien-Szymanska","year":"2014","journal-title":"PLoS ONE"},{"key":"2025071503483264600_BIO062010C32","doi-asserted-by":"publisher","first-page":"1226413","DOI":"10.3389\/fnmol.2023.1226413","article-title":"The role of microRNAs in neurobiology and pathophysiology of the hippocampus","volume":"16","author":"Rashidi","year":"2023","journal-title":"Front. Mol. Neurosci."},{"key":"2025071503483264600_BIO062010C33","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/s41467-023-44658-1","article-title":"hnRNP A1 dysfunction alters RNA splicing and drives neurodegeneration in multiple sclerosis (MS)","volume":"15","author":"Salapa","year":"2024","journal-title":"Nat. Commun."},{"key":"2025071503483264600_BIO062010C34","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.3390\/antiox11071374","article-title":"Alcohol-induced oxidative stress and the role of antioxidants in alcohol use disorder: a systematic review","volume":"11","author":"Tsermpini","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"2025071503483264600_BIO062010C35","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1083\/jcb.149.2.307","article-title":"The MKK(3\/6)-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation","volume":"149","author":"Van Der Houven Van Oordt","year":"2000","journal-title":"J. Cell Biol."},{"key":"2025071503483264600_BIO062010C36","doi-asserted-by":"publisher","first-page":"307","DOI":"10.3389\/fnmol.2017.00307","article-title":"Intermittent ethanol during adolescence leads to lasting behavioral changes in adulthood and alters gene expression and histone methylation in the PFC","volume":"10","author":"Wolstenholme","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"2025071503483264600_BIO062010C37","doi-asserted-by":"publisher","first-page":"101381","DOI":"10.1016\/j.redox.2019.101381","article-title":"Acetaldehyde induces phosphorylation of dynamin-related protein 1 and mitochondrial dysfunction via elevating intracellular ROS and Ca(2+) levels","volume":"28","author":"Yan","year":"2020","journal-title":"Redox Biol."}],"container-title":["Biology Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.062010\/3653262\/bio062010.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.062010\/3656740\/bio062010.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.062010\/3656740\/bio062010.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T07:48:38Z","timestamp":1752565718000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/bio\/article\/14\/7\/bio062010\/368578\/Ethanol-induces-subcellular-trafficking-of-the-RNA"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,15]]},"references-count":37,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7,15]]}},"URL":"https:\/\/doi.org\/10.1242\/bio.062010","relation":{},"ISSN":["2046-6390"],"issn-type":[{"type":"electronic","value":"2046-6390"}],"subject":[],"published":{"date-parts":[[2025,7,15]]},"article-number":"bio062010"}}