| Autor: |
Šušnjar, Urša, Škrabar, Neva, Brown, Anna-Leigh, Abbassi, Yasmine, Phatnani, Hemali, NYGC ALS Consortium, Phatnani, H., Fratta, P., Kwan, J., Sareen, D., Broach, J. R., Simmons, Z., Arcila-Londono, X., Lee, E. B., Van Deerlin, V. M., Shneider, N. A., Fraenkel, E., Ostrow, L. W., Baas, F., Berry, J. D. |
| Předmět: |
|
| Zdroj: |
Communications Biology; 4/5/2022, Vol. 5 Issue 1, p1-17, 17p |
| Abstrakt: |
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'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. The aetiology of the TDP-43 aggregation manifest itself in the muscle and neuronal cells. Here authors show cell-type characteristic functions of TDP43, reflected in aberrant splicing, likely contributing to disease development. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
