PQBP1 is a transient component of RNA splicing complex and presumably regulate splicing target hnRNAs that include transcripts from neural genes related to synapse functions or cell cycle genes related to stem cell proliferation. PQBP1 also interacts with RNA polymerase II at C-terminal tails when the specific sequences are phosphorylated during maturation of hnRNAs. PQBP1 is dominantly located in the nucleus of neurons for such nuclear functions, while it is also located in the cytoplasm innate immune cells such as dendritic cells and brain microglia. In these immune cells, PQBP1 plays a role of intracellular receptor for HIV virus cDNA/protein or Tau protein, a causative protein for neurodegeneration in Alzheimer’s disease and frontotemporal lobar degeneration.
PQBP1 gene mutations like decreased or increased number of dinuleotide repeat cause shifts of the amino acid reading frame, which truncate C-terminal intrinsically disordered region (IDR) or decrease the amount of protein due to RNA decay. It is known that C-terminal region interacts with U5-15kD, a component of U5 spliceosome. The gene mutation at the critical amino acid (Y65C) for the N-terminal WW domain, which is found in Golabi-Ito-Hall syndrome, impairs the WW-domain-mediated protein-protein interaction.
PQBP1