RNA-binding protein FUS

FUS (RNA-binding protein FUS) is a 526-amino acid DNA/RNA-binding protein that regulates transcription, RNA splicing, RNA transport, DNA repair, and damage responses (UniProt: P35637). It binds nascent pre-mRNAs and mediates coupling between RNA polymerase II and the spliceosome. In neurons, FUS plays critical roles in dendritic spine formation, RNA transport, mRNA stability, and synaptic homeostasis.

FUS is associated with amyotrophic lateral sclerosis (ALS6) and essential tremor as well as angiomatoid fibrous histiocytoma (UniProt: P35637). Mutations in FUS cause neurodegeneration characterized by motor neuron loss and pathologic protein aggregates, linking the protein to motor and neurodegenerative pathways.

In Alzheimer's disease, FUS is downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.44 (Chaparral AD proteomics). This reduction was measured via TMT-labeled data-dependent acquisition proteomics across subcellular fractions, suggesting diminished FUS availability may contribute to AD pathology, particularly given its roles in RNA metabolism and synaptic function.