140674 20240321220843.0 10.1016/j.jmb.2019.01.034 doi pmid:30711541 pmid 0022-2836 ISSN 1089-8638 ISSN altmetric:54814099 altmetric DZNE-2020-06996 English 610 Schilling, Judith P:(DE-2719)2810643 0 First author dzne Deregulated Splicing Is a Major Mechanism of RNA-Induced Toxicity in Huntington's Disease. Amsterdam [u.a.] 2019 Elsevier print Crossref Elsevier BV 2019-04-01 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1685011861_32155 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin (HTT) gene, translating into an elongated polyglutamine stretch. In addition to the neurotoxic mutant HTT protein, the mutant CAG repeat RNA can exert toxic functions by trapping RNA-binding proteins. While few examples of proteins that aberrantly bind to mutant HTT RNA and execute abnormal function in conjunction with the CAG repeat RNA have been described, an unbiased approach to identify the interactome of mutant HTT RNA is missing. Here, we describe the analysis of proteins that preferentially bind mutant HTT RNA using a mass spectrometry approach. We show that (I) the majority of proteins captured by mutant HTT RNA belong to the spliceosome pathway, (II) expression of mutant CAG repeat RNA induces mis-splicing in a HD cell model, (III) overexpression of one of the splice factors trapped by mutant HTT ameliorates the HD phenotype in a fly model and (VI) deregulated splicing occurs in human HD brain. Our data suggest that deregulated splicing is a prominent mechanism of RNA-induced toxicity in HD. 342 - Disease Mechanisms and Model Systems (POF3-342) G:(DE-HGF)POF3-342 POF3-342 POF III 0 341 - Molecular Signaling (POF3-341) G:(DE-HGF)POF3-341 POF3-341 POF III 1 2019-04-01 Crossref https://www.elsevier.com/tdm/userlicense/1.0/ 2019-02-02 Crossref http://creativecommons.org/licenses/by-nc-nd/4.0/ Dataset connected to CrossRef, PubMed, Animals MeSH Humans MeSH Huntingtin Protein: genetics MeSH Huntington Disease: genetics MeSH RNA: genetics MeSH RNA Splicing: genetics MeSH Spliceosomes: genetics MeSH Broemer, Meike P:(DE-2719)2810307 1 dzne Atanassov, Ilian 2 Dürnberger, Yvonne P:(DE-2719)2810519 3 dzne Vorberg, Ina P:(DE-2719)2481765 4 dzne Dieterich, Christoph 5 Dagane, Alina 6 Dittmar, Gunnar 7 Wanker, Erich 8 van Roon-Mom, Willeke 9 Winter, Jennifer 10 Krauß, Sybille P:(DE-2719)2421562 11 Last author dzne 10.1016/j.jmb.2019.01.034 : Elsevier BV, 2019-04-01 9 1869-1877 journal-article Crossref Journal of Molecular Biology 431 2019 0022-2836 10.1016/j.jmb.2019.01.034 Vol. 431, no. 9, p. 1869 - 1877 PERI:(DE-600)1355192-9 9 431:9<1869 - 1877 1869-1877 Journal of molecular biology 431 2019 0022-2836 OpenAccess http://pub.dzne.de/record/140674/files/DZNE-2020-06996.pdf OpenAccess pdfa http://pub.dzne.de/record/140674/files/DZNE-2020-06996.pdf?subformat=pdfa oai:pub.dzne.de:140674 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2810643 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2810307 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2810519 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 4 P:(DE-2719)2481765 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 11 P:(DE-2719)2421562 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-342 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Disease Mechanisms and Model Systems 0 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-341 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Molecular Signaling 1 2019 Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 LIC:(DE-HGF)CCBYNCND4 HGFVOC OpenAccess StatID:(DE-HGF)0510 StatID Nationallizenz StatID:(DE-HGF)0420 StatID 2022-11-08 ger JCR StatID:(DE-HGF)0100 StatID J MOL BIOL : 2021 2022-11-08 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-08 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-08 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-08 Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-08 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-08 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-08 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-08 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-08 IF >= 5 StatID:(DE-HGF)9905 StatID J MOL BIOL : 2021 2022-11-08 I:(DE-2719)1011006 AG Krauß ; AG Krauß Regulatory RNA-protein interaction in neurodegenerative diseases 0 I:(DE-2719)5000021 AG Brömer 1 ; AG Brömer 1 Ubiquitin-Mediated Processes in Neurodegenerative Diseases 1 I:(DE-2719)1013004 AG Vorberg Prion Cell Biology 2 journal VDB UNRESTRICTED I:(DE-2719)1011006 I:(DE-2719)5000021 I:(DE-2719)1013004 FullTexts