{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:15:38Z","timestamp":1787008538551,"version":"build-2736575974"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,6,13]],"date-time":"2020-06-13T00:00:00Z","timestamp":1592006400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"CIBERNED-ISCIII","award":["PI2015-2\/06-3"],"award-info":[{"award-number":["PI2015-2\/06-3"]}]},{"name":"CIBERNED-ISCIII","award":["PI2018\/06-1"],"award-info":[{"award-number":["PI2018\/06-1"]}]},{"name":"Spanish Ministry of Economy and Competitiveness"},{"name":"Ministry of Science"},{"name":"Innovation and Universities","award":["SAF2015-65371-R"],"award-info":[{"award-number":["SAF2015-65371-R"]}]},{"name":"Innovation and Universities","award":["RTI2018-096322-B-I00"],"award-info":[{"award-number":["RTI2018-096322-B-I00"]}]},{"name":"Innovation and Universities","award":["PI18\/00263"],"award-info":[{"award-number":["PI18\/00263"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministry of Economy, Industry and Competitiveness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008054","name":"Fundaci\u00f3n Ram\u00f3n Areces","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Huntington\u2019s disease and X-linked dystonia parkinsonism are two monogenic basal ganglia model diseases. Huntington\u2019s disease is caused by a polyglutamine-encoding CAG repeat expansion in the Huntingtin (HTT) gene leading to several toxic interactions of both the expanded CAG-containing mRNA and the polyglutamine-containing protein, while X-linked dystonia parkinsonism is caused by a retrotransposon insertion in the TAF1 gene, which decreases expression of this core scaffold of the basal transcription factor complex TFIID. SRSF6 is an RNA-binding protein of the serine and arginine-rich (SR) protein family that interacts with expanded CAG mRNA and is sequestered into the characteristic polyglutamine-containing inclusion bodies of Huntington\u2019s disease brains. Here we report decreased levels of the SRSF6 interactor and regulator SREK1\u2014another SR protein involved in RNA processing\u2014which includes TAF1 as one of its targets. This led us to hypothesize that Huntington\u2019s disease and X-linked dystonia parkinsonism pathogeneses converge in TAF1 alteration. We show that diminishing SRSF6 through RNA interference in human neuroblastoma cells leads to a decrease in SREK1 levels, which, in turn, suffices to cause diminished TAF1 levels. We also observed decreased SREK1 and TAF1 levels in striatum of Huntington\u2019s disease patients and transgenic model mice. We then generated mice with neuronal transgenic expression of SREK1 (TgSREK1 mice) that, interestingly, showed transcriptomic alterations complementary to those in Huntington\u2019s disease mice. Most importantly, by combining Huntington\u2019s disease and TgSREK1 mice we verify that SREK1 overexpression corrects TAF1 deficiency and attenuates striatal atrophy and motor phenotype of Huntington\u2019s disease mice. Our results therefore demonstrate that altered RNA processing upon SREK1 dysregulation plays a key role in Huntington\u2019s disease pathogenesis and pinpoint TAF1 as a likely general determinant of selective vulnerability of the striatum in multiple neurological disorders.<\/jats:p>","DOI":"10.1093\/brain\/awaa150","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T15:09:47Z","timestamp":1589296187000},"page":"2207-2219","source":"Crossref","is-referenced-by-count":26,"title":["Pathogenic SREK1 decrease in Huntington\u2019s disease lowers TAF1 mimicking X-linked dystonia parkinsonism"],"prefix":"10.1093","volume":"143","author":[{"given":"Iv\u00f3 H","family":"Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Center for Molecular Biology \u2018Severo Ochoa\u2019 (CBMSO) CSIC\/UAM, Madrid 28049, Spain"},{"name":"Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain"},{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias, Universidad Aut\u00f3noma de Madrid, Madrid 28049, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4481-0198","authenticated-orcid":false,"given":"Jorge R","family":"Cabrera","sequence":"first","affiliation":[{"name":"Center for Molecular Biology \u2018Severo Ochoa\u2019 (CBMSO) CSIC\/UAM, Madrid 28049, Spain"},{"name":"Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Santos-Galindo","sequence":"first","affiliation":[{"name":"Center for Molecular Biology \u2018Severo Ochoa\u2019 (CBMSO) CSIC\/UAM, Madrid 28049, Spain"},{"name":"Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"S\u00e1nchez-Mart\u00edn","sequence":"first","affiliation":[{"name":"Transgenic Facility, Nucleus platform, Universidad de Salamanca, Salamanca 37007, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Center for Molecular Biology \u2018Severo Ochoa\u2019 (CBMSO) CSIC\/UAM, Madrid 28049, Spain"},{"name":"Transgenesis Facility CNB-CBMSO, CSIC-UAM, Madrid 28049, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Garc\u00eda-Escudero","sequence":"first","affiliation":[{"name":"Molecular Oncology Unit, CIEMAT, Madrid 28040, Spain"},{"name":"Biomedicine Research Institute, Hospital 12 Octubre, Madrid 28041, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, Madrid 28029, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda J","family":"P\u00e9rez-\u00c1lvarez","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias, Universidad Aut\u00f3noma de Madrid, Madrid 28049, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8485-2520","authenticated-orcid":false,"given":"Bel\u00e9n","family":"Pintado","sequence":"first","affiliation":[{"name":"Transgenesis Facility CNB-CBMSO, CSIC-UAM, Madrid 28049, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1597-3916","authenticated-orcid":false,"given":"Jos\u00e9 J","family":"Lucas","sequence":"first","affiliation":[{"name":"Center for Molecular Biology \u2018Severo Ochoa\u2019 (CBMSO) CSIC\/UAM, Madrid 28049, Spain"},{"name":"Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, 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