PRPF31
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPRPF31, pre-mRNA processing factor 31, NY-BR-99, PRP31, RP11, SNRNP61
External IDsOMIM: 606419 MGI: 1916238 HomoloGene: 5980 GeneCards: PRPF31
Orthologs
SpeciesHumanMouse
Entrez

26121

68988

Ensembl

ENSG00000275885
ENSG00000105618

ENSMUSG00000008373

UniProt

Q8WWY3

Q8CCF0

RefSeq (mRNA)

NM_015629

NM_001159714
NM_027328

RefSeq (protein)

NP_056444
NP_056444.3

NP_001153186
NP_081604

Location (UCSC)Chr 19: 54.12 – 54.13 MbChr 7: 3.63 – 3.65 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5]

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.[6]

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.[7]

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.[5] 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.[8]

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.[9] 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.[10][11]

References

  1. 1 2 3 ENSG00000105618 GRCh38: Ensembl release 89: ENSG00000275885, ENSG00000105618 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000008373 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Vithana EN, Abu-Safieh L, Allen MJ, Carey A, Papaioannou M, Chakarova C, Al-Maghtheh M, Ebenezer ND, Willis C, Moore AT, Bird AC, Hunt DM, Bhattacharya SS (August 2001). "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. doi:10.1016/S1097-2765(01)00305-7. PMID 11545739.
  6. ↑ Schaffert N, Hossbach M, Heintzmann R, Achsel T, Lührmann R (August 2004). "RNAi knockdown of hPrp31 leads to an accumulation of U4/U6 di-snRNPs in Cajal bodies". EMBO J. 23 (15): 3000–9. doi:10.1038/sj.emboj.7600296. PMC 514917. PMID 15257298.
  7. ↑ Liu S, Li P, Dybkov O, Nottrott S, Hartmuth K, Lührmann R, Carlomagno T, Wahl MC (April 2007). "Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP". Science. 316 (5821): 115–20. Bibcode:2007Sci...316..115L. doi:10.1126/science.1137924. hdl:11858/00-001M-0000-0012-E16C-F. PMID 17412961. S2CID 22091845.
  8. ↑ "Entrez Gene: PRPF31 PRP31 pre-mRNA processing factor 31 homolog (S. cerevisiae)".
  9. ↑ Waseem NH, Vaclavik V, Webster A, Jenkins SA, Bird AC, Bhattacharya SS (March 2007). "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. doi:10.1167/iovs.06-0963. PMID 17325180.
  10. ↑ Randon J, Boulanger L, Marechal J, Garbarz M, Vallier A, Ribeiro L, Tamagnini G, Dhermy D, Delaunay J (Nov 1994). "A variant of spectrin low-expression allele alpha LELY carrying a hereditary elliptocytosis mutation in codon 28". Br J Haematol. 88 (3): 534–40. doi:10.1111/j.1365-2141.1994.tb05070.x. PMID 7819065. S2CID 39527747.
  11. ↑ Gouya L, Puy H, Lamoril J, Da Silva V, Grandchamp B, Nordmann Y, Deybach JC (Jun 1998). "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. PMID 10068685.

Further reading


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