TDP-43 and FUS/TLS: Cellular functions and implications for neurodegeneration

Fabienne C. Fiesel, Philipp J. Kahle

Research output: Contribution to journalReview article

55 Scopus citations

Abstract

TDP-43 (transactive response binding protein of 43 kDa) and FUS (fused in sarcoma) comprise the neuropathological protein aggregates of distinct subtypes of the neurodegenerative diseases frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Moreover, the genes encoding TDP-43 and FUS are linked to these diseases. Both TDP-43 and FUS contain RNA binding motifs, and specific targets are being identified. Potential actions of TDP-43 and FUS include transcriptional regulation, mRNA processing and micro RNA biogenesis. These activities are probably modulated by interacting proteins in cell type specific manners as well as distinctly within the nucleus and cytosol, as both proteins shuttle between these compartments. In this minireview the specific functions of TDP-43 and FUS are described and discussed in the context of how TDP-43 and FUS may contribute to the pathogenesis of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43 and FUS comprise the neuropathological protein aggregates of distinct subtypes of the neurodegenerative diseases frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Functions of the RNA-binding proteins TDP-43 and FUS include transcriptional regulation, mRNA processing and miRNA biogenesis. This minireview describes and discusses the specific functions of TDP-43 and FUS in the context of the pathogenesis of neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)3550-3568
Number of pages19
JournalFEBS Journal
Volume278
Issue number19
DOIs
StatePublished - Oct 2011

Keywords

  • ALS
  • FTLD
  • FUS
  • HDAC6
  • RNA
  • RNA metabolism
  • TDP-43
  • autophagy
  • splicing
  • transcription

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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