TY  - JOUR
AU  - Das, Richa
AU  - Schwintzer, Lukas
AU  - Vinopal, Stanislav
AU  - Aguado Roca, Eva
AU  - Sylvester, Marc
AU  - Oprisoreanu, Ana-Maria
AU  - Schoch, Susanne
AU  - Bradke, Frank
AU  - Broemer, Meike
TI  - New roles for the de-ubiquitylating enzyme OTUD4 in an RNA-protein network and RNA granules.
JO  - Journal of cell science
VL  - 132
IS  - 12
SN  - 0021-9533
CY  - Cambridge
PB  - Company of Biologists Limited
M1  - DZNE-2020-07104
SP  - jcs229252
PY  - 2019
AB  - 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.
KW  - Amyotrophic Lateral Sclerosis: metabolism
KW  - Animals
KW  - Cytoplasmic Granules: metabolism
KW  - DNA Helicases: genetics
KW  - DNA-Binding Proteins: metabolism
KW  - HeLa Cells
KW  - Humans
KW  - Mice, Inbred C57BL
KW  - Mutation: genetics
KW  - Neurodegenerative Diseases: genetics
KW  - Neurodegenerative Diseases: metabolism
KW  - Neurons: metabolism
KW  - RNA Recognition Motif Proteins: metabolism
KW  - Ubiquitin-Specific Proteases: genetics
KW  - Ubiquitin-Specific Proteases: metabolism
LB  - PUB:(DE-HGF)16
C6  - pmid:31138677
C2  - pmc:PMC6602300
DO  - DOI:10.1242/jcs.229252
UR  - https://pub.dzne.de/record/140782
ER  -