Cytoplasmic functions of TDP-43 and FUS and their role in ALS. (March 2020)

• Record Type: Journal Article
• Authors: Birsa, Nicol; Bentham, Matthew Peter; Fratta, Pietro
• Is Part Of: Seminars in cell & developmental biology. Volume 99(2020)
• Page Start: 193
• Page End: 201
• Publication Date: 2020-03
• Subjects: ALS amyotrophic lateral sclerosis -- FTD frontotemporal dementia -- FUS fused in sarcoma -- LCD low complexity domain -- LLPS liquid-liquid phase separation -- NLS nuclear localisation signal -- RBP RNA binding protein -- RNP ribonucleoprotein -- TDP-43 TAR DNA- binding protein -- UTR untranslated region; TDP-43 -- FUS -- ALS -- RNP -- Translation -- Stress granules; Cytology -- Periodicals; Developmental biology -- Periodicals; 571.6
• DOI: 10.1016/j.semcdb.2019.05.023
• Languages: English
• ISSNs: 1084-9521

Abstract

Abstract: 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.