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Alternative polyadenylation in the 3\u2019 untranslated region (3\u2019UTR) can alter RNA localization, stability and translational efficiency. The\n                    <jats:italic>SERPINA1<\/jats:italic>\n                    mRNA has two distinct 3\u2019 UTR isoforms, both of which express the protease inhibitor \u03b1-1-antitrypsin (A1AT). A1AT is an acute phase protein that is expressed and secreted from liver hepatocytes and upregulated during inflammation. Low levels of A1AT in the lung contributes to chronic obstructive pulmonary disease, while misfolding of A1AT in the liver contributes to liver cirrhosis. We analyzed the dynamics of alternative polyadenylation during cellular stress by treating the liver cell line HepG2 with the cytokine interleukin 6 (IL-6), ethanol or peroxide.\n                    <jats:italic>SERPINA1<\/jats:italic>\n                    is transcriptionally upregulated after IL-6 treatment and has altered polyadenylation, resulting in an increase in long 3\u2019UTR isoforms. We find that the long 3\u2019UTR represses endogenous A1AT protein expression even with high levels of\n                    <jats:italic>SERPINA1<\/jats:italic>\n                    mRNA.\n                    <jats:italic>SERPINA1<\/jats:italic>\n                    expression and 3\u2019 end processing are not affected by ethanol or peroxide. IL-6-induced changes in transcriptome-wide transcriptional regulation suggest changes to the endoplasmic reticulum and in secretory protein processing. Our data shows that inflammation influences polyA site choice for\n                    <jats:italic>SERPINA1<\/jats:italic>\n                    transcripts, resulting in reduced A1AT protein expression.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-07569-3","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T01:42:46Z","timestamp":1751420566000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Altered polyadenylation site usage in SERPINA1 3\u2019UTR in response to cellular stress affects A1AT protein expression"],"prefix":"10.1038","volume":"15","author":[{"given":"F. N. 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