140782 20240321220855.0 10.1242/jcs.229252 doi pmid:31138677 pmid pmc:PMC6602300 pmc 0021-9533 ISSN 0370-2952 ISSN 1477-9137 ISSN altmetric:61354383 altmetric DZNE-2020-07104 English 570 Das, Richa P:(DE-2719)2811341 0 First author dzne New roles for the de-ubiquitylating enzyme OTUD4 in an RNA-protein network and RNA granules. Cambridge 2019 Company of Biologists Limited online Crossref The Company of Biologists 2019-05-28 print Crossref The Company of Biologists 2019-06-15 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1687248253_3105 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Mechanisms that regulate the formation of membrane-less cellular organelles, such as neuronal RNA granules and stress granules, have gained increasing attention over the past years. These granules consist of RNA and a plethora of RNA-binding proteins. Mutations in RNA-binding proteins have been found in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). By performing pulldown experiments and subsequent mass spectrometry on mouse brain lysates, we discovered that the de-ubiquitylating enzyme OTU domain-containing protein 4 (OTUD4) unexpectedly is part of a complex network of multiple RNA-binding proteins, including core stress granule factors, such as FMRP (also known as FMR1), SMN1, G3BP1 and TIA1. We show that OTUD4 binds RNA, and that several of its interactions with RNA-binding proteins are RNA dependent. OTUD4 is part of neuronal RNA transport granules in rat hippocampal neurons under physiological conditions, whereas upon cellular stress, OTUD4 is recruited to cytoplasmic stress granules. Knockdown of OTUD4 in HeLa cells resulted in defects in stress granule formation and led to apoptotic cell death. Together, we characterize OTUD4 as a new RNA-binding protein with a suggested function in regulation of translation. 341 - Molecular Signaling (POF3-341) G:(DE-HGF)POF3-341 POF3-341 POF III 0 2019-06-17 Crossref http://creativecommons.org/licenses/by/4.0 Dataset connected to CrossRef, PubMed, Amyotrophic Lateral Sclerosis: metabolism MeSH Animals MeSH Cytoplasmic Granules: metabolism MeSH DNA Helicases: genetics MeSH DNA-Binding Proteins: metabolism MeSH HeLa Cells MeSH Humans MeSH Mice, Inbred C57BL MeSH Mutation: genetics MeSH Neurodegenerative Diseases: genetics MeSH Neurodegenerative Diseases: metabolism MeSH Neurons: metabolism MeSH RNA Recognition Motif Proteins: metabolism MeSH Ubiquitin-Specific Proteases: genetics MeSH Ubiquitin-Specific Proteases: metabolism MeSH Schwintzer, Lukas P:(DE-2719)2810987 1 dzne Vinopal, Stanislav P:(DE-2719)2810898 2 dzne Aguado Roca, Eva P:(DE-2719)2810320 3 dzne Sylvester, Marc 4 Oprisoreanu, Ana-Maria 5 Schoch, Susanne 6 Bradke, Frank P:(DE-2719)2810270 7 dzne Broemer, Meike P:(DE-2719)2810307 8 Last author dzne 10.1242/jcs.229252 : The Company of Biologists, 2019-05-28 12 jcs229252 journal-article Crossref Journal of Cell Science 132 2019 0021-9533 10.1242/jcs.229252 Vol. 132, no. 12, p. jcs229252 - PERI:(DE-600)1483099-1 12 132:12<jcs229252 - jcs229252 Journal of cell science 132 2019 0021-9533 https://journals.biologists.com/jcs/article/132/12/jcs229252/179/New-roles-for-the-de-ubiquitylating-enzyme-OTUD4 Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602300 VDB oai:pub.dzne.de:140782 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2811341 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2810987 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2810898 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2810320 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)2810270 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 8 P:(DE-2719)2810307 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 0 2019 JCR StatID:(DE-HGF)0100 StatID J CELL SCI : 2021 2022-11-11 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-11 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-11 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-11 Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-11 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-11 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-11 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-11 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-11 IF >= 5 StatID:(DE-HGF)9905 StatID J CELL SCI 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