PRPF31

PRP31 pre-mRNA processing factor 31 homolog (S. cerevisiae), also known as PRPF31, is a is_associated_with::protein which in humans is encoded by the PRPF31 is_associated_with::gene.

Function
PRPF31 is the gene coding for the is_associated_with::splicing factor hPRP31. It is essential for the formation of the is_associated_with::spliceosome hPRP31 is associated with the U4/U4 di-snRNP and interacts with another splicing factor, hPRP6, to form the U4/U6-U5 tri-snRNP. It has been shown that when hPRP31 is knocked down by RNAi, U4/U6 di-snPRNPs accumulate in the Cajal bodies and the U4/U6-U5 tri-snRNP cannot form.

PRPF31 is recruited to is_associated_with::introns following the attachment of U4 and U6 RNAs and the 15.5K protein is_associated_with::NHP2L1. The addition of PRPF31 is crucial for the transition of the spliceosomal complex to the activated state.

Clinical significance
A mutation in PRPF31 is one of 4 known mutations in splicing factors which are known to cause is_associated_with::retinitis pigmentosa. The first mutation in PRPF31 was discovered by Vithana et al. in 2001. Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies characterized by a progressive degeneration of photoreceptors, eventually resulting in severe visual impairment.

Inheritance
Mutations in PRPF31 are inherited in an is_associated_with::autosomal dominant manner, accounting for 2.5% of cases of is_associated_with::autosomal dominant is_associated_with::retinitis pigmentosa (adRP) in a mixed UK population. However, the inheritance pattern of PRPF31 mutations is atypical of dominant inheritance, showing the phenomenon of is_associated_with::partial penetrance, whereby a dominant mutations appear to "skip" generations. This is thought to be due to the presence of two is_associated_with::wild type alleles, a high-expressivity is_associated_with::allele and a low-expressivity allele. If a patient has a mutant allele and a high-expressivity allele, they do not show disease phenotype. If a patient has a mutant allele and a low-expressivity allele, the residual level of protein falls beneath the threahold for normal function, and so they do show disease phenotype. The inheritance pattern of PRPF31 can therefore be thought of as a variation of is_associated_with::haploinsufficiency. This variant of haploinsufficiency is only seen in two other human diseases: is_associated_with::Erythropoietic protoporphyria, caused by mutations in the FECH gene; and is_associated_with::hereditary elliptocytosis, caused by mutations in the is_associated_with::spectrin gene.