Format

Send to

Choose Destination
FEBS Lett. 2017 Jun;591(11):1489-1507. doi: 10.1002/1873-3468.12646. Epub 2017 Apr 23.

TDP-43 and FUS en route from the nucleus to the cytoplasm.

Author information

1
BioMedical Center (BMC), Ludwig-Maximilians-University Munich, Planegg-Martinsried, Germany.
2
Graduate School of Systemic Neurosciences (GSN), Planegg-Martinsried, Germany.
3
Munich Cluster for Systems Neurology (SyNergy), Germany.

Abstract

Misfolded or mislocalized RNA-binding proteins (RBPs) and, consequently, altered mRNA processing, can cause neuronal dysfunction, eventually leading to neurodegeneration. Two prominent examples are the RBPs TAR DNA-binding protein of 43 kDa (TDP-43) and fused in sarcoma (FUS), which form pathological messenger ribonucleoprotein aggregates in patients suffering from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating neurodegenerative disorders. Here, we review the multiple functions of TDP-43 and FUS in mRNA processing, both in the nucleus and in the cytoplasm. We discuss how TDP-43 and FUS may exit the nucleus and how defects in both nuclear and cytosolic mRNA processing events, and possibly nuclear export defects, may contribute to neurodegeneration and ALS/FTD pathogenesis.

KEYWORDS:

ALS ; FTD ; FUS/TLS; TDP-43; mRNA processing; mRNPs; neurodegeneration; nuclear export; nucleocytoplasmic transport

PMID:
28380257
DOI:
10.1002/1873-3468.12646
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center