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@ARTICLE{GarcaMorato:269004,
author = {García Morato, Jorge and Gloeckner, Christian Johannes and
Kahle, Philipp},
title = {{P}roteomics elucidating physiological and pathological
functions of {TDP}‐43},
journal = {Proteomics},
volume = {23},
number = {23-24},
issn = {1615-9853},
address = {Weinheim},
publisher = {Wiley VCH},
reportid = {DZNE-2024-00438},
pages = {2200410},
year = {2023},
abstract = {Trans-activation response DNA binding protein of 43 kDa
(TDP-43) regulates a great variety of cellular processes in
the nucleus and cytosol. In addition, a defined subset of
neurodegenerative diseases is characterized by nuclear
depletion of TDP-43 as well as cytosolic mislocalization and
aggregation. To perform its diverse functions TDP-43 can
associate with different ribonucleoprotein complexes.
Combined with transcriptomics, MS interactome studies have
unveiled associations between TDP-43 and the spliceosome
machinery, polysomes and RNA granules. Moreover, the highly
dynamic, low-valency interactions regulated by its
low-complexity domain calls for innovative proximity
labeling methodologies. In addition to protein partners, the
analysis of post-translational modifications showed that
they may play a role in the nucleocytoplasmic shuttling, RNA
binding, liquid-liquid phase separation and protein
aggregation of TDP-43. Here we review the various TDP-43
ribonucleoprotein complexes characterized so far, how they
contribute to the diverse functions of TDP-43, and roles of
post-translational modifications. Further understanding of
the fluid dynamic properties of TDP-43 in ribonucleoprotein
complexes, RNA granules, and self-assemblies will advance
the understanding of RNA processing in cells and perhaps
help to develop novel therapeutic approaches for
TDPopathies.},
subtyp = {Review Article},
keywords = {Proteomics / Protein Aggregates / DNA-Binding Proteins:
genetics / Ribonucleoproteins},
cin = {AG Gasser / AG Gloeckner},
ddc = {540},
cid = {I:(DE-2719)1210000 / I:(DE-2719)1210007},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37671599},
doi = {10.1002/pmic.202200410},
url = {https://pub.dzne.de/record/269004},
}