Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease

Front Biosci. 2008 Jan 1;13:867-78. doi: 10.2741/2727.


TDP-43 is a RNA/DNA binding protein that structurally resembles a typical hnRNP protein family member and displays a significant specificity for binding the common microsatellite region (GU/GT)n. Initially described as a regulator of HIV-1 gene expression, it has been reported in the past to affect both normal and pathological RNA splicing events. In particular, it has been shown to play a fundamental role in the occurrence of several monosymptomatic/full forms of Cystic Fibrosis caused by pathological skipping of CFTR exon 9 from the mature mRNA. Recently, and in a way probably unrelated to splicing, a hyperphosphorylated form of TDP-43 has also been found to accumulate in the cytoplasm of neuronal cells of patients affected by fronto temporal lobar degenerations. In addition to its role in transcription and splicing regulation, a growing body of evidence indirectly suggests that TDP-43 may be involved in other cellular processes such as microRNA biogenesis, apoptosis, and cell division. The aim of this work is to provide the basic facts about TDP-43 an assessment of the multiple functions ascribed to this protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing
  • Animals
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology*
  • Exons
  • Gene Expression
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Models, Biological
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • RNA Splicing*
  • RNA, Messenger / metabolism


  • DNA-Binding Proteins
  • RNA, Messenger