Pre-mRNA Processing Factor 40B (PRPF40B)

The hallmark neuropathology of Huntington's disease (HD) is due to elongation of a polyglutamine segment in huntingtin, a novel approximately 350 kDa protein of unknown function. Surprisingly, no interactors were found with internal and C-terminal segments of huntingtin. In contrast, huntingtin's N-terminus detected 13 distinct proteins, seven novel and six reported previously. Among these, identified a major interactor class, comprising three distinct WW domain proteins, HYPA, HYPB and HYPC, that bind normal and mutant huntingtin in extracts of HD lymphoblastoid cells. This interaction is mediated by huntingtin's proline-rich region and is enhanced by lengthening the adjacent glutamine tract. Although HYPB and HYPC are novel, HYPA is human FBP-11, a protein implicated in spliceosome function.