Gene Symbol: PRPF4
Description: pre-mRNA processing factor 4
Alias: HPRP4, HPRP4P, PRP4, Prp4p, RP70, SNRNP60, U4/U6 small nuclear ribonucleoprotein Prp4, PRP4 homolog, PRP4 pre-mRNA processing factor 4 homolog, PRP4/STK/WD splicing factor, U4/U6 snRNP 60 kDa protein, WD splicing factor Prp4
Species: human
Products:     PRPF4

Top Publications

  1. Lauber J, Plessel G, Prehn S, Will C, Fabrizio P, Gröning K, et al. The human U4/U6 snRNP contains 60 and 90kD proteins that are structurally homologous to the yeast splicing factors Prp4p and Prp3p. RNA. 1997;3:926-41 pubmed
    ..8% similarity, 33.9% identity) between the human 60kD protein and the Saccharomyces cerevisiae U4/U6 snRNP protein Prp4p. Two additional, previously undetected WD repeats (with seven in total) were also identified in Prp4p, consistent ..
  2. Horowitz D, Kobayashi R, Krainer A. A new cyclophilin and the human homologues of yeast Prp3 and Prp4 form a complex associated with U4/U6 snRNPs. RNA. 1997;3:1374-87 pubmed
    ..Two of the proteins are homologues of the Saccharomyces cerevisiae splicing factors Prp3 and Prp4, and the third protein is a cyclophilin. Both the human and S...
  3. Teigelkamp S, Achsel T, Mundt C, Göthel S, Cronshagen U, Lane W, et al. The 20kD protein of human [U4/U6.U5] tri-snRNPs is a novel cyclophilin that forms a complex with the U4/U6-specific 60kD and 90kD proteins. RNA. 1998;4:127-41 pubmed
    ..We discuss possible roles of SnuCyp-20 in the assembly of [U4/U6.U5] tri-snRNPs and/or in conformational changes occurring during the splicing process. ..
  4. Chen X, Liu Y, Sheng X, Tam P, Zhao K, Chen X, et al. PRPF4 mutations cause autosomal dominant retinitis pigmentosa. Hum Mol Genet. 2014;23:2926-39 pubmed publisher
    ..b>HPrp4, encoded by PRPF4, regulates the stability of U4/U6 di-snRNP, which is essential for continuous splicing...
  5. Kojima T, Zama T, Wada K, Onogi H, Hagiwara M. Cloning of human PRP4 reveals interaction with Clk1. J Biol Chem. 2001;276:32247-56 pubmed
    ..We cloned human PRP4 (hPRP4) full-length cDNA and the antiserum raised against a partial peptide of hPRP4 recognized 170-kDa polypeptide in ..
  6. Shakhmantsir I, Nayak S, Grant G, Sehgal A. Spliceosome factors target timeless (tim) mRNA to control clock protein accumulation and circadian behavior in Drosophila. elife. 2018;7: pubmed publisher
    ..Through an RNA interference screen, we found that pre-mRNA processing 4 (PRP4) kinase, a component of the U4/U5...
  7. Vachon C, Li J, Scott C, Hall P, Czene K, Wang X, et al. No evidence for association of inherited variation in genes involved in mitosis and percent mammographic density. Breast Cancer Res. 2012;14:R7 pubmed
    ..A variant in PRPF4, rs10733604, was significantly associated with adjusted PMD in the MCBCS (P = 2...
  8. Kanno T, Venhuizen P, Wen T, Lin W, Chiou P, Kalyna M, et al. PRP4KA, a Putative Spliceosomal Protein Kinase, Is Important for Alternative Splicing and Development in Arabidopsis thaliana. Genetics. 2018;210:1267-1285 pubmed publisher
    ..We report here the identification of pre-mRNA processing 4 (PRP4) KINASE A (PRP4KA) in a forward genetic screen based on an alternatively spliced GFP reporter gene in ..
  9. Wang Y, Han Y, Xu P, Ding S, Li G, Jin H, et al. prpf4 is essential for cell survival and posterior lateral line primordium migration in zebrafish. J Genet Genomics. 2018;45:443-453 pubmed publisher
    b>Prpf4 (pre-mRNA processing factor 4), a key component of spliceosome, plays critical roles in pre-mRNA splicing and its mutations result in retinitis pigmentosa due to photoreceptor defects...

More Information


  1. Islam S, Ahmed M, Lee S, Shehzad A, Sonn J, Kwon O, et al. PRP4 kinase induces actin rearrangement and epithelial-mesenchymal transition through modulation of the actin-binding protein cofilin. Exp Cell Res. 2018;369:158-165 pubmed publisher
    ..Pre-mRNA processing factor 4B (PRP4) modulates the actin cytoskeleton of cancer cells via RhoA activity inhibition...
  2. Gao X, Zhang J, Song C, Yuan K, Wang J, Jin Q, et al. Phosphorylation by Prp4 kinase releases the self-inhibition of FgPrp31 in Fusarium graminearum. Curr Genet. 2018;64:1261-1274 pubmed publisher
    ..The nonsense mutation at R464 in FgPRP31 resulted in the truncation of CT130 that contains all the putative Prp4 kinase-phosphorylation sites reported in humans, and partially rescued intron splicing defects of Fgprp4...
  3. Eckert D, Andrée N, Razanau A, Zock Emmenthal S, Lützelberger M, Plath S, et al. Prp4 Kinase Grants the License to Splice: Control of Weak Splice Sites during Spliceosome Activation. PLoS Genet. 2016;12:e1005768 pubmed publisher
    ..In this study, we further characterized another of these essential kinases, Prp4, and showed that the splicing of many introns is dependent on Prp4 kinase activity...
  4. Hardin J, Warnasooriya C, Kondo Y, Nagai K, Rueda D. Assembly and dynamics of the U4/U6 di-snRNP by single-molecule FRET. Nucleic Acids Res. 2015;43:10963-74 pubmed publisher
    ..The spliceosomal U4/U6 di-snRNP contains extensively base paired U4 and U6 snRNAs, Snu13, Prp31, Prp3 and Prp4, seven Sm and seven LSm proteins...
  5. Makarova O, Makarov E, Luhrmann R. The 65 and 110 kDa SR-related proteins of the U4/U6.U5 tri-snRNP are essential for the assembly of mature spliceosomes. EMBO J. 2001;20:2553-63 pubmed
    ..Moreover, since both proteins contain an N-terminal RS domain, they could mediate the association of the tri-snRNP with pre-spliceosomes by interaction with members of the SR protein family. ..
  6. Reidt U, Wahl M, Fasshauer D, Horowitz D, Luhrmann R, Ficner R. Crystal structure of a complex between human spliceosomal cyclophilin H and a U4/U6 snRNP-60K peptide. J Mol Biol. 2003;331:45-56 pubmed
  7. Schneider C, Will C, Makarova O, Makarov E, Luhrmann R. Human U4/U6.U5 and U4atac/U6atac.U5 tri-snRNPs exhibit similar protein compositions. Mol Cell Biol. 2002;22:3219-29 pubmed
  8. Stanek D, Neugebauer K. Detection of snRNP assembly intermediates in Cajal bodies by fluorescence resonance energy transfer. J Cell Biol. 2004;166:1015-25 pubmed
    ..U4/U6 snRNP in CBs. Thus, while some U4/U6 snRNP assembly can occur in the nucleoplasm, these data provide evidence that SART3.U6 snRNPs form in the nucleoplasm and translocate to CBs where U4/U6 snRNP assembly occurs...
  9. Huang B, Ahn Y, McPherson L, Clayberger C, Krensky A. Interaction of PRP4 with Kruppel-like factor 13 regulates CCL5 transcription. J Immunol. 2007;178:7081-7 pubmed
    ..Using yeast two-hybrid screening of a human thymus cDNA library, PRP4, a serine/threonine protein kinase, was identified as a KLF13-binding protein...
  10. Montembault E, Dutertre S, Prigent C, Giet R. PRP4 is a spindle assembly checkpoint protein required for MPS1, MAD1, and MAD2 localization to the kinetochores. J Cell Biol. 2007;179:601-9 pubmed
    ..In this study, we report that the human pre-messenger RNA processing 4 (PRP4) protein kinase associates with kinetochores during mitosis...
  11. Gao Q, Mechin I, Kothari N, Guo Z, Deng G, Haas K, et al. Evaluation of cancer dependence and druggability of PRP4 kinase using cellular, biochemical, and structural approaches. J Biol Chem. 2013;288:30125-38 pubmed publisher
    b>PRP4 kinase is known for its roles in regulating pre-mRNA splicing and beyond. Therefore, a wider spectrum of PRP4 kinase substrates could be expected. The role of PRP4 kinase in cancer is also yet to be fully elucidated...
  12. Horowitz D, Krainer A. A human protein required for the second step of pre-mRNA splicing is functionally related to a yeast splicing factor. Genes Dev. 1997;11:139-51 pubmed
    ..In contrast to yeast Prp18, hPrp18 is not stably associated with any of the snRNPs. A 55-kD protein that cross-reacts with antibodies against hPrp18 is a constituent of the U4/U6 and U4/U6 x U5 snRNP particles. ..
  13. Hart T, Chandrashekhar M, Aregger M, Steinhart Z, Brown K, Macleod G, et al. High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities. Cell. 2015;163:1515-26 pubmed publisher
    ..Thus, rigorous identification of human cell line fitness genes using a high-complexity CRISPR-Cas9 library affords a high-resolution view of the genetic vulnerabilities of a cell. ..
  14. Heng H, Wang A, Hu J. Mapping of the human HPRP3 and HPRP4 genes encoding U4/U6-associated splicing factors to chromosomes 1q21.1 and 9q31-q33. Genomics. 1998;48:273-5 pubmed
  15. Duan Z, Weinstein E, Ji D, Ames R, Choy E, Mankin H, et al. Lentiviral short hairpin RNA screen of genes associated with multidrug resistance identifies PRP-4 as a new regulator of chemoresistance in human ovarian cancer. Mol Cancer Ther. 2008;7:2377-85 pubmed publisher
    ..Finally, overexpression of PRP-4 in drug-sensitive cells could induce a modest level of drug resistance to paclitaxel, doxorubicin, and vincristine. ..
  16. Ingelfinger D, Göthel S, Marahiel M, Reidt U, Ficner R, Luhrmann R, et al. Two protein-protein interaction sites on the spliceosome-associated human cyclophilin CypH. Nucleic Acids Res. 2003;31:4791-6 pubmed
  17. Wang A, Forman Kay J, Luo Y, Luo M, Chow Y, Plumb J, et al. Identification and characterization of human genes encoding Hprp3p and Hprp4p, interacting components of the spliceosome. Hum Mol Genet. 1997;6:2117-26 pubmed
    ..the identification and characterization of two human genes encoding U4/U6-associated splicing factors, Hprp3p and Hprp4p, respectively...
  18. Linder B, Hirmer A, Gal A, Rüther K, Bolz H, Winkler C, et al. Identification of a PRPF4 loss-of-function variant that abrogates U4/U6.U5 tri-snRNP integration and is associated with retinitis pigmentosa. PLoS ONE. 2014;9:e111754 pubmed publisher
    ..Mutations in six spliceosomal proteins, PRPF3, PRPF4, PRPF6, PRPF8, PRPF31 and SNRNP200, cause retinitis pigmentosa (RP), a disease characterized by progressive ..
  19. Pabis M, Neufeld N, Steiner M, Bojic T, Shav Tal Y, Neugebauer K. The nuclear cap-binding complex interacts with the U4/U6·U5 tri-snRNP and promotes spliceosome assembly in mammalian cells. RNA. 2013;19:1054-63 pubmed publisher
    ..Among these, three U4/U6·U5 snRNP proteins (hBrr2, hPrp4, and hPrp31) copurified with CBC in an RNA-independent fashion, suggesting that a significant fraction of CBC ..
  20. Bertram K, Agafonov D, Dybkov O, Haselbach D, Leelaram M, Will C, et al. Cryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for Activation. Cell. 2017;170:701-713.e11 pubmed publisher
    ..Our results indicate significant differences between the early activation phase of human and yeast spliceosomes. ..
  21. Bennett E, Lever A, Allen J. Human immunodeficiency virus type 2 Gag interacts specifically with PRP4, a serine-threonine kinase, and inhibits phosphorylation of splicing factor SF2. J Virol. 2004;78:11303-12 pubmed
    ..cellular proteins that bind to the human immunodeficiency virus type 2 (HIV-2) Gag polyprotein, we identified PRP4, a serine-threonine protein kinase...
  22. Gonzalez Santos J, Wang A, Jones J, Ushida C, Liu J, Hu J. Central region of the human splicing factor Hprp3p interacts with Hprp4p. J Biol Chem. 2002;277:23764-72 pubmed
    Human splicing factors Hprp3p and Hprp4p are associated with the U4/U6 small nuclear ribonucleoprotein particle, which is essential for the assembly of an active spliceosome...
  23. Fukami J, Ollero F, Megias M, Hungria M. Phytohormones and induction of plant-stress tolerance and defense genes by seed and foliar inoculation with Azospirillum brasilense cells and metabolites promote maize growth. AMB Express. 2017;7:153 pubmed publisher
    ..related to oxidative stress (APX1, APX2, CAT1, SOD2, SOD4) and plant defense (pathogenesis-related PR1, prp2 and prp4) was evaluated on maize leaves and roots...
  24. Rajiv C, Jackson S, Cocklin S, Eisenmesser E, Davis T. The spliceosomal proteins PPIH and PRPF4 exhibit bi-partite binding. Biochem J. 2017;474:3689-3704 pubmed publisher
    ..peptidyl-prolyl isomerase H (PPIH) directly interacts with the core protein pre-mRNA processing factor 4 (PRPF4) and both integrate into the pre-catalytic spliceosome as part of the tri-snRNP (small nuclear RNA-protein complex)..
  25. Liu S, Rauhut R, Vornlocher H, Luhrmann R. The network of protein-protein interactions within the human U4/U6.U5 tri-snRNP. RNA. 2006;12:1418-30 pubmed
    ..Taken together, data presented here provide a detailed picture of the network of protein interactions within the human tri-snRNP. ..
  26. Schaffert N, Hossbach M, Heintzmann R, Achsel T, Luhrmann R. RNAi knockdown of hPrp31 leads to an accumulation of U4/U6 di-snRNPs in Cajal bodies. EMBO J. 2004;23:3000-9 pubmed
    ..In contrast, U5 snRNPs largely remain in nucleoplasmic speckles. Our data support the idea that CBs may play a role in tri-snRNP recycling. ..