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@ARTICLE{Das:140782,
author = {Das, Richa and Schwintzer, Lukas and Vinopal, Stanislav and
Aguado Roca, Eva and Sylvester, Marc and Oprisoreanu,
Ana-Maria and Schoch, Susanne and Bradke, Frank and Broemer,
Meike},
title = {{N}ew roles for the de-ubiquitylating enzyme {OTUD}4 in an
{RNA}-protein network and {RNA} granules.},
journal = {Journal of cell science},
volume = {132},
number = {12},
issn = {0021-9533},
address = {Cambridge},
publisher = {Company of Biologists Limited},
reportid = {DZNE-2020-07104},
pages = {jcs229252},
year = {2019},
abstract = {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.},
keywords = {Amyotrophic Lateral Sclerosis: metabolism / Animals /
Cytoplasmic Granules: metabolism / DNA Helicases: genetics /
DNA-Binding Proteins: metabolism / HeLa Cells / Humans /
Mice, Inbred C57BL / Mutation: genetics / Neurodegenerative
Diseases: genetics / Neurodegenerative Diseases: metabolism
/ Neurons: metabolism / RNA Recognition Motif Proteins:
metabolism / Ubiquitin-Specific Proteases: genetics /
Ubiquitin-Specific Proteases: metabolism},
cin = {AG Brömer 1 ; AG Brömer 1 / AG Bradke ; AG Bradke},
ddc = {570},
cid = {I:(DE-2719)5000021 / I:(DE-2719)1013002},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31138677},
pmc = {pmc:PMC6602300},
doi = {10.1242/jcs.229252},
url = {https://pub.dzne.de/record/140782},
}