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 significanceedit
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]
Inheritanceedit
Mutations in PRPF31 are inherited in an autosomal dominant manner, accounting for 2.5% of cases of autosomal dominantretinitis 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]
^ abcGRCm38: Ensembl release 89: ENSMUSG00000008373 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abVithana 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.
^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. PMC514917. PMID 15257298.
^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.
^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.
^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.
^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 readingedit
Tarizzo ML (1975). "The World Health Organization and the prevention of blindness". Transactions. Section on Ophthalmology. American Academy of Ophthalmology and Otolaryngology. 79 (3 Pt 2): OP453–6. PMID 1154573.
al-Maghtheh M, Inglehearn CF, Keen TJ, et al. (1994). "Identification of a sixth locus for autosomal dominant retinitis pigmentosa on chromosome 19". Hum. Mol. Genet. 3 (2): 351–4. doi:10.1093/hmg/3.2.351. PMID 8004108.
Al-Maghtheh M, Vithana E, Tarttelin E, et al. (1996). "Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11) and association with a unique bimodal expressivity phenotype". Am. J. Hum. Genet. 59 (4): 864–71. PMC1914817. PMID 8808602.
Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC310948. PMID 11076863.
Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC311072. PMID 11230166.
Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC1083732. PMID 11256614.
Vithana EN, Abu-Safieh L, Allen MJ, et al. (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.
Makarova OV, Makarov EM, Liu S, et al. (2002). "Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6·U5 tri-snRNP formation and pre-mRNA splicing". EMBO J. 21 (5): 1148–57. doi:10.1093/emboj/21.5.1148. PMC125353. PMID 11867543.
Deery EC, Vithana EN, Newbold RJ, et al. (2003). "Disease mechanism for retinitis pigmentosa (RP11) caused by mutations in the splicing factor gene PRPF31". Hum. Mol. Genet. 11 (25): 3209–19. doi:10.1093/hmg/11.25.3209. PMID 12444105.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
Martínez-Gimeno M, Gamundi MJ, Hernan I, et al. (2003). "Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa". Invest. Ophthalmol. Vis. Sci. 44 (5): 2171–7. doi:10.1167/iovs.02-0871. PMID 12714658.
Scanlan MJ, Gout I, Gordon CM, et al. (2003). "Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression". Cancer Immun. 1: 4. PMID 12747765.
Wang L, Ribaudo M, Zhao K, et al. (2003). "Novel Deletion in the Pre-mRNA Splicing Gene PRPF31 Causes Autosomal Dominant Retinitis Pigmentosa in a Large Chinese Family". Am. J. Med. Genet. A. 121 (3): 235–9. doi:10.1002/ajmg.a.20224. PMC1579744. PMID 12923864.
Reuter TY, Medhurst AL, Waisfisz Q, et al. (2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Exp. Cell Res. 289 (2): 211–21. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622.
Vithana EN, Abu-Safieh L, Pelosini L, et al. (2003). "Expression of PRPF31 mRNA in patients with autosomal dominant retinitis pigmentosa: a molecular clue for incomplete penetrance?". Invest. Ophthalmol. Vis. Sci. 44 (10): 4204–9. doi:10.1167/iovs.03-0253. PMID 14507862.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Grimwood J, Gordon LA, Olsen A, et al. (2004). "The DNA sequence and biology of human chromosome 19". Nature. 428 (6982): 529–35. Bibcode:2004Natur.428..529G. doi:10.1038/nature02399. PMID 15057824.
Xia K, Zheng D, Pan Q, et al. (2004). "A novel PRPF31 splice-site mutation in a Chinese family with autosomal dominant retinitis pigmentosa". Mol. Vis. 10: 361–5. PMID 15162096.
Schaffert N, Hossbach M, Heintzmann R, et al. (2005). "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. PMC514917. PMID 15257298.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC528928. PMID 15489334.
External linksedit
GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview
January 01, 1970
prpf31, prp31, mrna, processing, factor, homolog, cerevisiae, also, known, protein, which, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes2ozb, 3siu, 3siv, 3jcr, s3jcridentifiersaliases, mrna, processing, factor, prp31, r. 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 PRPF31Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes2OZB 3SIU 3SIV 3JCR s3JCRIdentifiersAliasesPRPF31 pre mRNA processing factor 31 NY BR 99 PRP31 RP11 SNRNP61External IDsOMIM 606419 MGI 1916238 HomoloGene 5980 GeneCards PRPF31Gene location Human Chr Chromosome 19 human 1 Band19q13 42Start54 115 410 bp 1 End54 131 719 bp 1 Gene location Mouse Chr Chromosome 7 mouse 2 Band7 7 A1Start3 632 984 bp 2 End3 645 485 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed instromal cell of endometriumganglionic eminenceplacentafunduscanal of the cervixright adrenal glandmonocyteright lobe of thyroid glandbody of stomachgastrocnemius muscleTop expressed inprimitive streakyolk sachair folliclemaxillary prominenceabdominal wallsomitesuperior frontal gyrusrenal corpusclemedullary collecting ductventromedial nucleusMore reference expression dataBioGPSn aGene ontologyMolecular functionsnRNP binding U4 snRNA binding U4atac snRNA binding protein binding ribonucleoprotein complex binding RNA bindingCellular componentCajal body nuclear speck U4 U6 x U5 tri snRNP complex U4atac snRNP nucleoplasm MLL1 complex U2 type spliceosomal complex precatalytic spliceosome spliceosomal complex U4 snRNP nucleus U2 type precatalytic spliceosomeBiological processmRNA splicing via spliceosome spliceosomal tri snRNP complex assembly mRNA processing snoRNA localization ribonucleoprotein complex localization RNA splicingSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez2612168988EnsemblENSG00000275885ENSG00000105618ENSMUSG00000008373UniProtQ8WWY3Q8CCF0RefSeq mRNA NM 015629NM 001159714NM 027328RefSeq protein NP 056444NP 056444 3NP 001153186NP 081604Location UCSC Chr 19 54 12 54 13 MbChr 7 3 63 3 65 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 Inheritance 4 References 5 Further reading 6 External linksFunction editPRPF31 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 editA 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 editMutations 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 edit a b c ENSG00000105618 GRCh38 Ensembl release 89 ENSG00000275885 ENSG00000105618 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000008373 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b 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 Schaffert N Hossbach M Heintzmann R Achsel T Luhrmann 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 Liu S Li P Dybkov O Nottrott S Hartmuth K Luhrmann 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 Entrez Gene PRPF31 PRP31 pre mRNA processing factor 31 homolog S cerevisiae 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 amp Visual Science 48 3 1330 4 doi 10 1167 iovs 06 0963 PMID 17325180 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 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 editTarizzo ML 1975 The World Health Organization and the prevention of blindness Transactions Section on Ophthalmology American Academy of Ophthalmology and Otolaryngology 79 3 Pt 2 OP453 6 PMID 1154573 al Maghtheh M Inglehearn CF Keen TJ et al 1994 Identification of a sixth locus for autosomal dominant retinitis pigmentosa on chromosome 19 Hum Mol Genet 3 2 351 4 doi 10 1093 hmg 3 2 351 PMID 8004108 Al Maghtheh M Vithana E Tarttelin E et al 1996 Evidence for a major retinitis pigmentosa locus on 19q13 4 RP11 and association with a unique bimodal expressivity phenotype Am J Hum Genet 59 4 864 71 PMC 1914817 PMID 8808602 Hartley JL Temple GF Brasch MA 2001 DNA Cloning Using In Vitro Site Specific Recombination Genome Res 10 11 1788 95 doi 10 1101 gr 143000 PMC 310948 PMID 11076863 Wiemann S Weil B Wellenreuther R et al 2001 Toward a Catalog of Human Genes and Proteins Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs Genome Res 11 3 422 35 doi 10 1101 gr GR1547R PMC 311072 PMID 11230166 Simpson JC Wellenreuther R Poustka A et al 2001 Systematic subcellular localization of novel proteins identified by large scale cDNA sequencing EMBO Rep 1 3 287 92 doi 10 1093 embo reports kvd058 PMC 1083732 PMID 11256614 Vithana EN Abu Safieh L Allen MJ et al 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 Makarova OV Makarov EM Liu S et al 2002 Protein 61K encoded by a gene PRPF31 linked to autosomal dominant retinitis pigmentosa is required for U4 U6 U5 tri snRNP formation and pre mRNA splicing EMBO J 21 5 1148 57 doi 10 1093 emboj 21 5 1148 PMC 125353 PMID 11867543 Deery EC Vithana EN Newbold RJ et al 2003 Disease mechanism for retinitis pigmentosa RP11 caused by mutations in the splicing factor gene PRPF31 Hum Mol Genet 11 25 3209 19 doi 10 1093 hmg 11 25 3209 PMID 12444105 Strausberg RL Feingold EA Grouse LH et al 2003 Generation and initial analysis of more than 15 000 full length human and mouse cDNA sequences Proc Natl Acad Sci U S A 99 26 16899 903 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Martinez Gimeno M Gamundi MJ Hernan I et al 2003 Mutations in the pre mRNA splicing factor genes PRPF3 PRPF8 and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa Invest Ophthalmol Vis Sci 44 5 2171 7 doi 10 1167 iovs 02 0871 PMID 12714658 Scanlan MJ Gout I Gordon CM et al 2003 Humoral immunity to human breast cancer antigen definition and quantitative analysis of mRNA expression Cancer Immun 1 4 PMID 12747765 Wang L Ribaudo M Zhao K et al 2003 Novel Deletion in the Pre mRNA Splicing Gene PRPF31 Causes Autosomal Dominant Retinitis Pigmentosa in a Large Chinese Family Am J Med Genet A 121 3 235 9 doi 10 1002 ajmg a 20224 PMC 1579744 PMID 12923864 Reuter TY Medhurst AL Waisfisz Q et al 2003 Yeast two hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation cell signaling oxidative metabolism and cellular transport Exp Cell Res 289 2 211 21 doi 10 1016 S0014 4827 03 00261 1 PMID 14499622 Vithana EN Abu Safieh L Pelosini L et al 2003 Expression of PRPF31 mRNA in patients with autosomal dominant retinitis pigmentosa a molecular clue for incomplete penetrance Invest Ophthalmol Vis Sci 44 10 4204 9 doi 10 1167 iovs 03 0253 PMID 14507862 Ota T Suzuki Y Nishikawa T et al 2004 Complete sequencing and characterization of 21 243 full length human cDNAs Nat Genet 36 1 40 5 doi 10 1038 ng1285 PMID 14702039 Grimwood J Gordon LA Olsen A et al 2004 The DNA sequence and biology of human chromosome 19 Nature 428 6982 529 35 Bibcode 2004Natur 428 529G doi 10 1038 nature02399 PMID 15057824 Xia K Zheng D Pan Q et al 2004 A novel PRPF31 splice site mutation in a Chinese family with autosomal dominant retinitis pigmentosa Mol Vis 10 361 5 PMID 15162096 Schaffert N Hossbach M Heintzmann R et al 2005 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 Gerhard DS Wagner L Feingold EA et al 2004 The Status Quality and Expansion of the NIH Full Length cDNA Project The Mammalian Gene Collection MGC Genome Res 14 10B 2121 7 doi 10 1101 gr 2596504 PMC 528928 PMID 15489334 External links editGeneReviews NCBI NIH UW entry on Retinitis Pigmentosa Overview Retrieved from https en wikipedia org w index php title PRPF31 amp oldid 1171071229, wikipedia, wiki, book, books, library,
