@article{b7f7d7faa70c4594b905555431b93394,
title = "Cell environment shapes TDP-43 function with implications in neuronal and muscle disease",
abstract = "TDP-43 (TAR DNA-binding protein 43) aggregation and redistribution are recognised as a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. As TDP-43 inclusions have recently been described in the muscle of inclusion body myositis patients, this highlights the need to understand the role of TDP-43 beyond the central nervous system. Using RNA-seq, we directly compare TDP-43-mediated RNA processing in muscle (C2C12) and neuronal (NSC34) mouse cells. TDP-43 displays a cell-type-characteristic behaviour targeting unique transcripts in each cell-type, which is due to characteristic expression of RNA-binding proteins, that influence TDP-43{\textquoteright}s performance and define cell-type specific splicing. Among splicing events commonly dysregulated in both cell lines, we identify some that are TDP-43-dependent also in human cells. Inclusion levels of these alternative exons are altered in tissues of patients suffering from FTLD and IBM. We therefore propose that TDP-43 dysfunction contributes to disease development either in a common or a tissue-specific manner.",
author = "{NYGC ALS Consortium} and Ur{\v s}a {\v S}u{\v s}njar and Neva {\v S}krabar and Brown, {Anna Leigh} and Yasmine Abbassi and Hemali Phatnani and H. Phatnani and P. Fratta and J. Kwan and D. Sareen and Broach, {J. R.} and Z. Simmons and X. Arcila-Londono and Lee, {E. B.} and {Van Deerlin}, {V. M.} and Shneider, {N. A.} and E. Fraenkel and Ostrow, {L. W.} and F. Baas and Berry, {J. D.} and O. Butovsky and Baloh, {R. H.} and Ophir Shalem and T. Heiman-Patterson and L. Stefanis and S. Chandran and S. Pal and C. Smith and A. Malaspina and Hammell, {M. G.} and Patsopoulos, {N. A.} and J. Dubnau and M. Poss and B. Zhang and N. Zaitlen and E. Hornstein and Miller, {T. M.} and E. Dardiotis and R. Bowser and V. Menon and M. Harms and N. Atassi and Lange, {D. J.} and MacGowan, {D. J.} and C. McMillan and E. Aronica and B. Harris and J. Ravits and J. Crary and Thompson, {L. M.} and T. Raj",
note = "Funding Information: We thank Marc-David Ruepp (King{\textquoteright}s College London) for providing RH-30 cells and Robert Bakari{\'c} for his kind assistance with the conservation analysis. We would also like to thank the Target ALS Human Postmortem Tissue Core (New York Genome Center for Genomics of Neurodegenerative Disease, Amyotrophic Lateral Sclerosis Association) for providing post-mortem brain samples, patients and their families who donated those samples. IBM muscle biopsies were kindly provided by the Bank of muscle tissue, peripheral nerve, DNA and Cell Culture, a member of Telethon Network of Genetic biobanks, at Fondazione IRCCS Ca{\textquoteright} Granda, Ospedale Maggiore Policlinico, Milano, Italy and from the Laboratory of Muscle Histopathology and Molecular Biology at IRCCS Policlinico San Donato, San Donato Milanese, Italy. This research was supported by the AriSLA grant PathensTDP to E. Bur. and by the European Reference Network for Neuromuscular Diseases to M. M. and M. Ro. Consortium activities were supported by the ALS Association (15-LGCA-234) and the Tow Foundation. G. M. was supported by Fondazione Malattie Miotoniche, Milan, Italy. Andrea Cortese would like to thank the Medical Research Council (MR/T001712/1), Cariplo Foundation, the Italian Ministry of Health (Ricerca Corrente 2018–2019), the Inherited Neuropathy Consortium and the Fondazione Regionale per la Ricerca Biomedica for the grant support. Funding Information: We thank Marc-David Ruepp (King{\textquoteright}s College London) for providing RH-30 cells and Robert Bakari{\'c} for his kind assistance with the conservation analysis. We would also like to thank the Target ALS Human Postmortem Tissue Core (New York Genome Center for Genomics of Neurodegenerative Disease, Amyotrophic Lateral Sclerosis Association) for providing post-mortem brain samples, patients and their families who donated those samples. IBM muscle biopsies were kindly provided by the Bank of muscle tissue, peripheral nerve, DNA and Cell Culture, a member of Telethon Network of Genetic biobanks, at Fondazione IRCCS Ca{\textquoteright} Granda, Ospedale Maggiore Policlinico, Milano, Italy and from the Laboratory of Muscle Histopathology and Molecular Biology at IRCCS Policlinico San Donato, San Donato Milanese, Italy. This research was supported by the AriSLA grant PathensTDP to E. Bur. and by the European Reference Network for Neuromuscular Diseases to M. M. and M. Ro. Consortium activities were supported by the ALS Association (15-LGCA-234) and the Tow Foundation. G. M. was supported by Fondazione Malattie Miotoniche, Milan, Italy. Andrea Cortese would like to thank the Medical Research Council (MR/T001712/1), Cariplo Foundation, the Italian Ministry of Health (Ricerca Corrente 2018–2019), the Inherited Neuropathy Consortium and the Fondazione Regionale per la Ricerca Biomedica for the grant support. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s42003-022-03253-8",
language = "English (US)",
volume = "5",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}