{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:04:19Z","timestamp":1783951459835,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,9]]},"group-title":"Neuroscience","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"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":[[2026,7,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of cellular identity and disease associated gene expression programs, yet their role in astrocyte reactivity remains poorly understood. Here, we profiled lncRNA expression in primary mouse astrocytes exposed to inflammatory activation paradigms that model microglia driven signaling. This identified a conserved set of activation responsive lncRNAs, among which\n                  <jats:italic>Gm16685<\/jats:italic>\n                  emerged as one of the most strongly induced candidates.\n                  <jats:italic>Gm16685<\/jats:italic>\n                  and its human homolog\n                  <jats:italic>MITA1<\/jats:italic>\n                  were enriched in the nucleus, and\n                  <jats:italic>MITA1<\/jats:italic>\n                  expression was increased in selected human datasets from Alzheimer\u2019s disease, Parkinson\u2019s disease and frontotemporal dementia patients. Functional depletion of\n                  <jats:italic>Gm16685<\/jats:italic>\n                  attenuated inflammatory gene expression and several activation associated astrocyte phenotypes, including reactive oxygen species production, glutamate handling, phagocytic activity and proliferation. Time-resolved transcriptomic analysis indicated that\n                  <jats:italic>Gm16685<\/jats:italic>\n                  is required for the timely induction of inflammatory response genes. Mechanistically,\n                  <jats:italic>Gm16685<\/jats:italic>\n                  \/\n                  <jats:italic>MITA1<\/jats:italic>\n                  interacted with the RNA binding protein PCBP2, and\n                  <jats:italic>Gm16685<\/jats:italic>\n                  depletion was associated with reduced PCBP2 protein abundance, altered splicing of Inhibitor of NF-\u03baB Kinase Subunit Beta (IKK\u03b2) and a shift in downstream inflammatory signaling. Together, our findings identify\n                  <jats:italic>Gm16685<\/jats:italic>\n                  \/\n                  <jats:italic>MITA1<\/jats:italic>\n                  as a conserved lncRNA regulator of astrocyte reactivity and suggest that non-coding RNA dependent control of RNA binding proteins contributes to inflammatory signaling in neurodegenerative disease relevant contexts.\n                <\/jats:p>","DOI":"10.64898\/2026.07.03.736437","type":"posted-content","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:45:34Z","timestamp":1783619134000},"source":"Crossref","is-referenced-by-count":0,"title":["The lncRNA\n                  <i>Gm16685<\/i>\n                  \/\n                  <i>MITA1<\/i>\n                  modulates inflammatory astrocyte reactivity through PCBP2 associated regulation of IKK\u03b2 signaling"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1201-0466","authenticated-orcid":false,"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"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7589-657X","authenticated-orcid":false,"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9329-8912","authenticated-orcid":false,"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2123-7694","authenticated-orcid":false,"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8546-1161","authenticated-orcid":false,"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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