Human FUS is toxic via association with RNA polymerase II in Drosophila - PubMed
4 hours ago
- #Neurodegeneration
- #FUS protein
- #RNA polymerase II
- Human FUS protein toxicity in Drosophila is linked to its association with RNA polymerase II.
- Overexpression of wild-type human FUS is toxic to Drosophila neurons, affecting development and lifespan.
- Removal of FUS's nuclear localization sequence (NLS) prevents toxicity despite causing cytoplasmic mislocalization.
- FUS forms dynamic protein granules in Drosophila nuclei and does not form insoluble aggregates.
- FUS interacts with the C-terminal domain (CTD) of RNA polymerase II (Polr2A), contributing to toxicity.
- Genetic interaction between FUS and Polr2A CTD is demonstrated in Drosophila models.
- Cytoplasmic mislocalization of POLR2A (human Polr2A orthologue) is observed in FUS-positive FTLD but not ALS-FUS.
- FUS toxicity in animal models involves a nuclear mechanism via RNA polymerase II interaction.
- Aberrant FUS-POLR2A interaction may play a role in FTLD pathogenesis.