PRP31 pre-mRNA processing factor 31 homolog (S. cerevisiae), also known as PRPF31, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
which in humans is encoded by the ''PRPF31''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
PRPF31 is the gene coding for the
splicing factor hPRP31. It is essential for the formation of the
spliceosome
A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs ( snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to sp ...
hPRP31 is associated with the
U4/
U6 di-snRNP and interacts with another splicing factor, h
PRP6, to form the U4/U6-
U5 tri-snRNP. It has been shown that when hPRP31 is knocked down by
RNAi, U4/U6 di-snRNPs accumulate in the
Cajal bodies and the U4/U6-U5 tri-snRNP cannot form.
PRPF31 is recruited to
intron
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...
s following the attachment of U4 and U6 RNAs and the 15.5K protein
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
retinitis pigmentosa
Retinitis pigmentosa (RP) is a member of a group of genetic disorders called inherited retinal dystrophy (IRD) that cause loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visua ...
. 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
autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
manner, accounting for 2.5% of cases of
autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
retinitis pigmentosa
Retinitis pigmentosa (RP) is a member of a group of genetic disorders called inherited retinal dystrophy (IRD) that cause loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visua ...
(adRP) in a mixed UK population.
However, the inheritance pattern of PRPF31 mutations is atypical of dominant inheritance, showing the phenomenon of
partial penetrance, whereby a dominant mutations appear to "skip" generations. This is thought to be due to the presence of two
wild type
The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, " ...
alleles, a high-expressivity
allele
An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule.
Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...
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 threshold for normal function, and so they do show disease phenotype. The inheritance pattern of PRPF31 can therefore be thought of as a variation of
haploinsufficiency
Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...
. This variant of haploinsufficiency is only seen in two other human diseases:
Erythropoietic protoporphyria
Erythropoietic protoporphyria (or commonly called EPP) is a form of porphyria, which varies in severity and can be very painful. It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the ...
, caused by mutations in the
FECH gene; and
hereditary elliptocytosis
Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the person's red blood cells are elliptical rather than the typical biconcave disc shape. Such morphologically distinctiv ...
, caused by mutations in the
spectrin
Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma mem ...
gene.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview
{{Post transcriptional modification
Spliceosome