Biology:PRPF31

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

PRP31 pre-mRNA processing factor 31 homolog (S. cerevisiae), also known as PRPF31, is a protein which in humans is encoded by the PRPF31 gene.[1]

Function

PRPF31 is the gene coding for the splicing factor hPRP31. It is essential for the formation of the spliceosome hPRP31 is associated with the U4/U6 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-snRNPs accumulate in the Cajal bodies and the U4/U6-U5 tri-snRNP cannot form.[2]

PRPF31 is recruited to introns 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.[3]

Clinical significance

A mutation in PRPF31 is one of 4 known mutations in splicing factors which are known to cause retinitis pigmentosa. The first mutation in PRPF31 was discovered by Vithana et al. in 2001.[1] 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.[4]

Inheritance

Mutations in PRPF31 are inherited in an autosomal dominant manner, accounting for 2.5% of cases of autosomal dominant retinitis pigmentosa (adRP) in a mixed UK population.[5] 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 alleles, a high-expressivity 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 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. This variant of haploinsufficiency is only seen in two other human diseases: Erythropoietic protoporphyria, caused by mutations in the FECH gene; and hereditary elliptocytosis, caused by mutations in the spectrin gene.[6][7]

References

  1. ↑ 1.0 1.1 "A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11)". Mol. Cell 8 (2): 375–81. August 2001. doi:10.1016/S1097-2765(01)00305-7. PMID 11545739. 
  2. ↑ "RNAi knockdown of hPrp31 leads to an accumulation of U4/U6 di-snRNPs in Cajal bodies". EMBO J. 23 (15): 3000–9. August 2004. doi:10.1038/sj.emboj.7600296. PMID 15257298. 
  3. ↑ "Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP". Science 316 (5821): 115–20. April 2007. doi:10.1126/science.1137924. PMID 17412961. Bibcode: 2007Sci...316..115L. 
  4. ↑ "Entrez Gene: PRPF31 PRP31 pre-mRNA processing factor 31 homolog (S. cerevisiae)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=26121. 
  5. ↑ "Mutations in the gene coding for the pre-mRNA splicing factor, PRPF31, in patients with autosomal dominant retinitis pigmentosa". Investigative Ophthalmology & Visual Science 48 (3): 1330–4. March 2007. doi:10.1167/iovs.06-0963. PMID 17325180. 
  6. ↑ "A variant of spectrin low-expression allele alpha LELY carrying a hereditary elliptocytosis mutation in codon 28". Br J Haematol 88 (3): 534–40. Nov 1994. doi:10.1111/j.1365-2141.1994.tb05070.x. PMID 7819065. 
  7. ↑ "Inheritance in erythropoietic protoporphyria: a common wild-type ferrochelatase allelic variant with low expression accounts for clinical manifestation". Am J Hum Genet 93 (6): 2150–10. Jun 1998. PMID 10068685. 

Further reading

External links





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