title: TDP-43 and FUS en route from the nucleus to the cytoplasm.
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.
authors.affiliation: BioMedical Center (BMC), Ludwig-Maximilians-University Munich, Planegg-Martinsried, Germany.|Graduate School of Systemic Neurosciences (GSN), Planegg-Martinsried, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Ederle
authors.affiliation: BioMedical Center (BMC), Ludwig-Maximilians-University Munich, Planegg-Martinsried, Germany.|Graduate School of Systemic Neurosciences (GSN), Planegg-Martinsried, Germany.|Munich Cluster for Systems Neurology (SyNergy), Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Dormann
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000599550:FUS protein, human; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; C000598624:TARDBP protein, human
keywords: 
  ALS
  ; 
  FTD
  ; FUS/TLS; TDP-43; mRNA processing; mRNPs; neurodegeneration; nuclear export; nucleocytoplasmic transport