The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Stress Induces Dynamic, Cytotoxicity-Antagonizing TDP-43 Nuclear Bodies via Paraspeckle LncRNA NEAT1-Mediated Liquid-Liquid Phase Separation
Open accessAbstract
Despite the prominent role of TDP-43 in neurodegeneration, its physiological and pathological functions are not fully understood. Here, we report an unexpected role of TDP-43 in the formation of dynamic, reversible, liquid droplet-like nuclear bodies (NBs) in response to stress. Formation of NBs alleviates TDP-43-mediated cytotoxicity in mammalian cells and fly neurons. Super-resolution microscopy reveals distinct functions of the two RRMs in TDP-43 NB formation. TDP-43 NBs are partially colocalized with nuclear paraspeckles, whose scaffolding lncRNA NEAT1 is dramatically upregulated in stressed neurons. Moreover, increase of NEAT1 promotes TDP-43 liquid-liquid phase separation (LLPS) in vitro. Finally, we discover that the ALS-associated mutation D169G impairs the NEAT1-mediated TDP-43 LLPS and NB assembly, causing excessive cytoplasmic translocation of TDP-43 to form stress granules, which become phosphorylated TDP-43 cytoplasmic foci upon prolonged stress. Together, our findings suggest a stress-mitigating role and mechanism of TDP-43 NBs, whose dysfunction may be involved in ALS pathogenesis.
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Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
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Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43
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Neuronal vulnerability and multilineage diversity in multiple sclerosis
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Cited by
HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells
Yu, H., Lu, S., Gasior, K., Singh, D., Vazquez-Sanchez, S., Tapia, O., Toprani, D., Beccari, M. S., Yates, J. R., Da Cruz, S., et al. (2021) · Science · doi:10.1126/science.abb4309 · Cited by 353
Disease‐linked TDP‐43 hyperphosphorylation suppresses TDP‐43 condensation and aggregation
Gruijs da Silva, L. A., Simonetti, F., Hutten, S., Riemenschneider, H., Sternburg, E. L., Pietrek, L. M., Gebel, J., Dötsch, V., Edbauer, D., Hummer, G., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2021108443 · Cited by 192
Long Non-Coding RNA (lncRNA) Roles in Cell Biology, Neurodevelopment and Neurological Disorders
Aliperti, V., Skonieczna, J., & Cerase, A. (2021) · Non-Coding RNA · doi:10.3390/ncrna7020036 · Cited by 137
Metadata
- Authors
- Wang, C., Duan, Y., Duan, G., Wang, Q., Zhang, K., Deng, X., Qian, B., Gu, J., Ma, Z., Zhang, S., Guo, L., Liu, C., & Fang, Y.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 79
- Issue
- 3
- Pages
- 443-458.e7
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W3041849832
- Cited by
- 230
- References
- 9
- FWCI
- 9.74
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Wang, C., Duan, Y., Duan, G., Wang, Q., Zhang, K., Deng, X., Qian, B., Gu, J., Ma, Z., Zhang, S., Guo, L., Liu, C., & Fang, Y. (2020). Stress Induces Dynamic, Cytotoxicity-Antagonizing TDP-43 Nuclear Bodies via Paraspeckle LncRNA NEAT1-Mediated Liquid-Liquid Phase Separation. Molecular Cell. https://doi.org/10.1016/j.molcel.2020.06.019
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