{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:21:36Z","timestamp":1787008896033,"version":"build-2736575974"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002243","name":"National Ataxia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K99 NS124994"],"award-info":[{"award-number":["K99 NS124994"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 NS04843"],"award-info":[{"award-number":["P50 NS04843"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS135254"],"award-info":[{"award-number":["R01 NS135254"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of rare dominantly inherited neurodegenerative diseases characterized by progressive ataxia. The most common mutation seen across the SCAs is a CAG repeat expansion, causative for SCA1, 2, 3, 6, 7, 12 and 17. We recently identified dysregulation of alternative splicing as a novel, presymptomatic transcriptomic hallmark in mouse models of SCAs 1, 3 and 7. In order to understand if dysregulation of alternative splicing is a transcriptomic feature of patient-derived cell models of CAG SCAs, we performed RNA sequencing and transcriptomic analysis in patient-derived fibroblast cell lines of SCAs 1, 3 and 7. We identified widespread and robust dysregulation of alternative splicing across all CAG expansion SCA lines investigated, with disease relevant pathways affected, such as microtubule-based processes, transcriptional regulation, and DNA damage and repair. Novel disease-relevant alternative splicing events were validated across patient-derived fibroblast lines from multiple CAG SCAs and CAG containing reporter cell lines. Together this study demonstrates that dysregulation of alternative splicing represents a novel and shared pathogenic process in CAG expansion SCA1, 3 and 7 and can potentially be used as a biomarker across patient models of this group of devastating neurodegenerative diseases.<\/jats:p>","DOI":"10.1093\/hmg\/ddae174","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T15:37:13Z","timestamp":1732289833000},"page":"239-250","source":"Crossref","is-referenced-by-count":5,"title":["Dysregulation of alternative splicing is a transcriptomic feature of patient-derived fibroblasts from CAG repeat expansion spinocerebellar ataxias"],"prefix":"10.1093","volume":"34","author":[{"given":"Asmer","family":"Aliyeva","sequence":"first","affiliation":[{"name":"RNA Institute, University at Albany, State University of New York , 1400 Washington Avenue, Albany, NY 12222 ,","place":["United States"]},{"name":"Department of Biological Sciences, University at Albany, 1400 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