Journal
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 99, Issue -, Pages 193-201Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2019.05.023
Keywords
TDP-43; FUS; ALS; RNP; Translation; Stress granules
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Funding
- MRC/MNDA LEW Fellowship
- NIHR-UCLH Biomedical Research Centre
- Rosetrees Foundation
- Wolfson PhD fellowship
- MRC [G1000287, MR/M008606/1, MR/S006508/1] Funding Source: UKRI
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TAR DNA-binding protein of 43 kDa (TDP-43) and fused in sarcoma (FUS) are RNA binding proteins (RBPs) primarily located in the nucleus, and involved in numerous aspects of RNA metabolism. Both proteins can be found to be depleted from the nucleus and accumulated in cytoplasmic inclusions in two major neurodegenerative conditions, amyotrophic lateral sclerosis and frontotemporal dementia. Recent evidences suggest that, in addition to their nuclear functions, both TDP-43 and FUS are involved in multiple processes in the cytoplasm, including mRNA stability and transport, translation, the stress response, mitochondrial function and autophagy regulation. Here, we review the most recent advances in understanding their functions in the cytoplasm and how these are affected in disease.
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