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@ARTICLE{Mori:136809,
author = {Mori, Kohji and Lammich, Sven and Mackenzie, Ian R A and
Forné, Ignasi and Zilow, Sonja and Kretzschmar, Hans and
Edbauer, Dieter and Janssens, Jonathan and Kleinberger,
Gernot and Cruts, Marc and Herms, Jochen and Neumann,
Manuela and Van Broeckhoven, Christine and Arzberger, Thomas
and Haass, Christian},
title = {hn{RNP} {A}3 binds to {GGGGCC} repeats and is a constituent
of p62-positive/{TDP}43-negative inclusions in the
hippocampus of patients with {C}9orf72 mutations.},
journal = {Acta neuropathologica},
volume = {125},
number = {3},
issn = {0001-6322},
address = {Heidelberg},
publisher = {Springer},
reportid = {DZNE-2020-03131},
pages = {413-423},
year = {2013},
abstract = {Genetic analysis revealed the hexanucleotide repeat
expansion GGGGCC within the regulatory region of the gene
C9orf72 as the most common cause of familial amyotrophic
lateral sclerosis and the second most common cause of
frontotemporal lobar degeneration. Since repeat expansions
might cause RNA toxicity via sequestration of RNA-binding
proteins, we searched for proteins capable of binding to
GGGGCC repeats. In vitro-transcribed biotinylated RNA
containing hexanucleotide GGGGCC or, as control, AAAACC
repeats were incubated with nuclear protein extracts. Using
stringent filtering protocols 20 RNA-binding proteins with a
variety of different functions in RNA metabolism,
translation and transport were identified. A subset of these
proteins was further investigated by immunohistochemistry in
human autopsy brains. This revealed that hnRNP A3 formed
neuronal cytoplasmic and intranuclear inclusions in the
hippocampus of patients with C9orf72 repeat extensions.
Confocal microcopy showed that these inclusions belong to
the group of the so far enigmatic p62-positive/TDP-43
negative inclusions characteristically seen in autopsy cases
of diseased C9orf72 repeat expansion carriers. Thus, we have
identified one protein component of these pathognomonic
inclusions.},
keywords = {Adaptor Proteins, Signal Transducing: metabolism /
Amyotrophic Lateral Sclerosis: genetics / Amyotrophic
Lateral Sclerosis: metabolism / Amyotrophic Lateral
Sclerosis: pathology / C9orf72 Protein / Chromatography,
High Pressure Liquid / DNA-Binding Proteins: metabolism /
Frontotemporal Lobar Degeneration: genetics / Frontotemporal
Lobar Degeneration: metabolism / Frontotemporal Lobar
Degeneration: pathology / Gene Expression Regulation:
genetics / HEK293 Cells / Heterogeneous-Nuclear
Ribonucleoprotein Group A-B: metabolism / Hippocampus:
pathology / Humans / Inclusion Bodies: metabolism /
Inclusion Bodies: pathology / Mass Spectrometry / Mutation:
genetics / Proteins: genetics / RNA, Small Interfering:
metabolism / Repetitive Sequences, Nucleic Acid: physiology
/ Sequestosome-1 Protein / Transfection / Adaptor Proteins,
Signal Transducing (NLM Chemicals) / C9orf72 Protein (NLM
Chemicals) / C9orf72 protein, human (NLM Chemicals) /
DNA-Binding Proteins (NLM Chemicals) / HNRNPA3 protein,
human (NLM Chemicals) / Heterogeneous-Nuclear
Ribonucleoprotein Group A-B (NLM Chemicals) / Proteins (NLM
Chemicals) / RNA, Small Interfering (NLM Chemicals) / SQSTM1
protein, human (NLM Chemicals) / Sequestosome-1 Protein (NLM
Chemicals)},
cin = {AG Edbauer / AG Herms / AG Neumann},
ddc = {610},
cid = {I:(DE-2719)1110004 / I:(DE-2719)1110001 /
I:(DE-2719)1210003},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
- Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23381195},
doi = {10.1007/s00401-013-1088-7},
url = {https://pub.dzne.de/record/136809},
}