Proteomic analyses reveal that loss of TDP-43 affects RNA processing and intracellular transport

M. Štalekar, X. Yin, K. Rebolj, S. Darovic, C. Troakes, M. Mayr, C. E. Shaw, B. Rogelj*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Transactive response DNA-binding protein 43 (TDP-43) is a predominantly nuclear, ubiquitously expressed RNA and DNA-binding protein. It recognizes and binds to UG repeats and is involved in pre-mRNA splicing, mRNA stability and microRNA metabolism. TDP-43 is essential in early embryonic development but accumulates in cytoplasmic aggregates in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal lobar degeneration (FTLD). It is not known yet whether cytoplasmic aggregates of TDP-43 are toxic or protective but they are often associated with a loss of TDP-43 from the nucleus and neurodegeneration may be caused by a loss of normal TDP-43 function or a gain of toxic function. Here we present a proteomic study to analyze the effect of loss of TDP-43 on the proteome. MS data are available via ProteomeXchange with identifier PXD001668. Our results indicate that TDP-43 is an important regulator of RNA metabolism and intracellular transport. We show that Ran-binding protein 1 (RanBP1), DNA methyltransferase 3 alpha (Dnmt3a) and chromogranin B (CgB) are downregulated upon TDP-43 knockdown. Subsequently, transportin 1 level is increased as a result of RanBP1 depletion. Improper regulation of these proteins and the subsequent disruption of cellular processes may play a role in the pathogenesis of the TDP-43 proteinopathies ALS and FTLD.

Original languageEnglish
Pages (from-to)157-170
Number of pages14
Publication statusPublished - 7 May 2015


  • Amyotrophic lateral sclerosis
  • Comparative proteomics
  • Frontotemporal lobar degeneration
  • Intracellular transport
  • RanBP1
  • TDP-43


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