Sep 22, 2009

TDP-43 is recruited to stress granules in conditions of oxidative insult

Journal of Neurochemistry
Claudia ColombritaAntonia Ratti

Abstract

Transactive response DNA-binding protein 43 (TDP-43) forms abnormal ubiquitinated and phosphorylated inclusions in brain tissues from patients with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. TDP-43 is a DNA/RNA-binding protein involved in RNA processing, such as transcription, pre-mRNA splicing, mRNA stabilization and transport to dendrites. We found that in response to oxidative stress and to environmental insults of different types TDP-43 is capable to assemble into stress granules (SGs), ribonucleoprotein complexes where protein synthesis is temporarily arrested. We demonstrated that a specific aminoacidic interval (216-315) in the C-terminal region and the RNA-recognition motif 1 domain are both implicated in TDP-43 participation in SGs as their deletion prevented the recruitment of TDP-43 into SGs. Our data show that TDP-43 is a specific component of SGs and not of processing bodies, although we proved that TDP-43 is not necessary for SG formation, and its gene silencing does not impair cell survival during stress. The analysis of spinal cord tissue from ALS patients showed that SG markers are not entrapped in TDP-43 pathological inclusions. Although SGs were not evident in ALS brains, we sp...Continue Reading

  • References42
  • Citations170

References

Mentioned in this Paper

TARDBP gene
Pre-mRNA Splicing
Transfection
Abnormal Degeneration
Emetine Dihydrochloride
Carboxy-Terminal Amino Acid
Ribonucleoprotein Activity
Ubiquitin
Malignant Neoplasm of Spinal Cord
Complex (molecular entity)

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