{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T20:14:22Z","timestamp":1783455262815,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,3]]},"group-title":"Neuroscience","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,3]]},"abstract":"<jats:p>\n                  Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of brain cell function, but their roles in astrocyte biology and neurodegeneration remain poorly understood. Here, we identify\n                  <jats:italic>Sox1ot\/SOX1-OT<\/jats:italic>\n                  as a conserved, brain-enriched lncRNA that is downregulated in Alzheimer\u2019s disease and in reactive astrocyte states. Antisense oligonucleotide-mediated depletion of\n                  <jats:italic>Sox1ot<\/jats:italic>\n                  in astrocytes revealed a transcriptional program marked by activation of p53 target genes selectively associated with cell-cycle inhibitory pathways. Consistent with this,\n                  <jats:italic>Sox1ot<\/jats:italic>\n                  depletion enhanced p53 occupancy at target promoters such as\n                  <jats:italic>Cdkn1a<\/jats:italic>\n                  , increased\n                  <jats:italic>Cdkn1a<\/jats:italic>\n                  expression and levels of its protein product p21, and thereby induced G1 arrest and reduced astrocyte proliferation. In contrast, other canonical p53 outputs, including apoptosis and senescence, were not affected, indicating that\n                  <jats:italic>Sox1ot<\/jats:italic>\n                  selectively modulates distinct branches of p53 signaling. Notably, loss of\n                  <jats:italic>Sox1ot\/SOX1-OT<\/jats:italic>\n                  was accompanied by impaired glutamate uptake, reduced lactate secretion, and altered astrocyte support functions, suggesting that these deficits arise as downstream consequences of the p53-dependent transcriptional shift rather than direct primary effects of\n                  <jats:italic>Sox1ot<\/jats:italic>\n                  loss. Together, these findings identify\n                  <jats:italic>SOX1-OT<\/jats:italic>\n                  as an astrocyte-enriched regulatory layer that constrains a p53-dependent cell-cycle program and highlight its role in shaping astrocyte state transitions in Alzheimer\u2019s disease.\n                <\/jats:p>","DOI":"10.64898\/2026.07.03.736275","type":"posted-content","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T07:50:12Z","timestamp":1783151412000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of the lncRNA\n                  <i>SOX1-OT<\/i>\n                  promotes p53-dependent cell-cycle arrest in astrocytes"],"prefix":"10.64898","author":[{"given":"Ulrike","family":"Fuchs","sequence":"first","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonatiuh","family":"Pena","sequence":"additional","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"},{"name":"Bioinformatics Unit, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis M","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"},{"name":"Bioinformatics Unit, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"},{"name":"Research Group for Genome Dynamics in Brain Diseases, German Center for Neurodegenerative Diseases, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Burkhardt","sequence":"additional","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"Sch\u00fctz","sequence":"additional","affiliation":[{"name":"Research Group for Genome Dynamics in Brain Diseases, German Center for Neurodegenerative Diseases, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Hempel","sequence":"additional","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Gisa","sequence":"additional","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarannom","family":"Taghavi","sequence":"additional","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Cortes","sequence":"additional","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gertig","sequence":"additional","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Delalle","sequence":"additional","affiliation":[{"name":"Boston University Alzheimer\u2019s Disease Research Center, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA"},{"name":"Cluster of Excellence \u201cMultiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells\u201d (MBExC), University of G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farahnaz","family":"Sananbenesi","sequence":"additional","affiliation":[{"name":"Research Group for Genome Dynamics in Brain Diseases, German Center for Neurodegenerative Diseases, G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), G\u00f6ttingen, Germany"},{"name":"Cluster of Excellence \u201cMultiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells\u201d (MBExC), University of G\u00f6ttingen, G\u00f6ttingen, Germany"},{"name":"Department of Psychiatry and Psychotherapy, University Medical Center G\u00f6ttingen, G\u00f6ttingen, 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