Cytoplasmic functions of TDP-43 and FUS and their role in ALS.

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.

• Authors: Nicol Birsa, Matthew Peter Bentham, Pietro Fratta
• Journal: Seminars in cell & developmental biology (Semin Cell Dev Biol) Vol. 99 Pg. 193-201 (03 2020) ISSN: 1096-3634 [Electronic] England
• PMID: 31132467 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2019. Published by Elsevier Ltd.

Chemical References

• DNA-Binding Proteins
• FUS protein, human
• RNA-Binding Protein FUS
• TARDBP protein, human

Topics

• Amyotrophic Lateral Sclerosis (metabolism)
• Cytoplasm (metabolism)
• DNA-Binding Proteins (metabolism)
• Humans
• RNA-Binding Protein FUS (metabolism)