u4 u6 small nuclear ribonucleoprotein


Summary: A nuclear RNA-protein complex that plays a role in RNA processing. In the nucleoplasm, the U4-U6 snRNP along with the U5 snRNP preassemble into a single 25S particle that binds to the U1 and U2 snRNPs and the substrate to form mature SPLICEOSOMES. There is also evidence for the existence of individual U4 or U6 snRNPs in addition to their organization as a U4-U6 snRNP.

Top Publications

  1. Rappsilber J, Ajuh P, Lamond A, Mann M. SPF30 is an essential human splicing factor required for assembly of the U4/U5/U6 tri-small nuclear ribonucleoprotein into the spliceosome. J Biol Chem. 2001;276:31142-50 pubmed
  2. Query C, Konarska M. Suppression of multiple substrate mutations by spliceosomal prp8 alleles suggests functional correlations with ribosomal ambiguity mutants. Mol Cell. 2004;14:343-54 pubmed
    ..This mechanistic commonality suggests that alteration of rearrangements represents an evolutionarily convenient way of modulating substrate selectivity. ..
  3. Achsel T, Brahms H, Kastner B, Bachi A, Wilm M, Luhrmann R. A doughnut-shaped heteromer of human Sm-like proteins binds to the 3'-end of U6 snRNA, thereby facilitating U4/U6 duplex formation in vitro. EMBO J. 1999;18:5789-802 pubmed
    ..Finally, we show that the LSm proteins facilitate the formation of U4/U6 RNA duplices in vitro, suggesting that the LSm proteins may play a role in U4/U6 snRNP formation. ..
  4. 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
    ..The third protein in the complex is a new cyclophilin. Cyclophilins have been proposed to act as chaperones in a variety of cellular processes, and we discuss some possible roles of this U4/U6 snRNP-associated cyclophilin. ..
  5. Lemm I, Girard C, Kuhn A, Watkins N, Schneider M, Bordonné R, et al. Ongoing U snRNP biogenesis is required for the integrity of Cajal bodies. Mol Biol Cell. 2006;17:3221-31 pubmed
    ..Altogether, our data suggest that CBs have a modular structure with distinct domains for spliceosomal U snRNPs and snoRNPs. ..
  6. Vidal V, Verdone L, Mayes A, Beggs J. Characterization of U6 snRNA-protein interactions. RNA. 1999;5:1470-81 pubmed
    ..Interestingly, the Lsm proteins associate efficiently with the 3' half of U6, which contains the 3' stem-loop and uridine-rich 3' end, suggesting that the Lsm and Sm proteins may recognize similar features in RNAs. ..
  7. Boon K, Norman C, Grainger R, Newman A, Beggs J. Prp8p dissection reveals domain structure and protein interaction sites. RNA. 2006;12:198-205 pubmed
    ..Thus, the U5 snRNP protein Snu114p associates with Prp8p in the region 437-770, whereas fragmenting Prp8p at residue 2173 destabilizes its association with Aar2p. ..
  8. Laggerbauer B, Achsel T, Luhrmann R. The human U5-200kD DEXH-box protein unwinds U4/U6 RNA duplices in vitro. Proc Natl Acad Sci U S A. 1998;95:4188-92 pubmed
    ..The RNA unwinding activity was found to reside exclusively with the U5-200kD DEXH-box protein. Our data raise the interesting possibility that this RNA helicase catalyzes unwinding of the U4/U6 RNA duplex in the spliceosome. ..
  9. 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. ..

More Information


  1. Anthony J, Weidenhammer E, Woolford J. The yeast Prp3 protein is a U4/U6 snRNP protein necessary for integrity of the U4/U6 snRNP and the U4/U6.U5 tri-snRNP. RNA. 1997;3:1143-52 pubmed
    ..U5 tri-snRNPs. Prp3p is homologous to a human protein that is a component of U4/U6 snRNPs, exemplifying the conservation of splicing factors between yeast and metazoans. ..
  2. Bottner C, Schmidt H, Vogel S, Michele M, Käufer N. Multiple genetic and biochemical interactions of Brr2, Prp8, Prp31, Prp1 and Prp4 kinase suggest a function in the control of the activation of spliceosomes in Schizosaccharomyces pombe. Curr Genet. 2005;48:151-61 pubmed
    ..These data are consistent with the notion that in fission yeast phosphorylation of Prp1 by Prp4 kinase is involved in the activation of pre-catalytic spliceosomes. ..
  3. Maeder C, Kutach A, Guthrie C. ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8. Nat Struct Mol Biol. 2009;16:42-8 pubmed publisher
    ..Because Brr2 activity must be restricted to prevent premature catalytic activation, our results have important implications for fidelity maintenance in the spliceosome. ..
  4. Stevens S, Barta I, Ge H, Moore R, Young M, Lee T, et al. Biochemical and genetic analyses of the U5, U6, and U4/U6 x U5 small nuclear ribonucleoproteins from Saccharomyces cerevisiae. RNA. 2001;7:1543-53 pubmed
    ..We also show that, unlike the human tri-snRNP, the yeast tri-snRNP dissociated upon addition of ATP or dATP. ..
  5. Brenner T, Guthrie C. Genetic analysis reveals a role for the C terminus of the Saccharomyces cerevisiae GTPase Snu114 during spliceosome activation. Genetics. 2005;170:1063-80 pubmed
    ..We propose that GTP hydrolysis results in a rearrangement between Prp8 and the C terminus of Snu114 that leads to release of U1 and U4, thus activating the spliceosome for catalysis. ..
  6. Kuhn A, Reichl E, Brow D. Distinct domains of splicing factor Prp8 mediate different aspects of spliceosome activation. Proc Natl Acad Sci U S A. 2002;99:9145-9 pubmed
    ..Furthermore, additional genetic interactions with U4-cs1 support a two-state model for this RNA conformational switch and implicate another splicing factor, Prp31, in Prp8-mediated spliceosome activation. ..
  7. Bellare P, Kutach A, Rines A, Guthrie C, Sontheimer E. Ubiquitin binding by a variant Jab1/MPN domain in the essential pre-mRNA splicing factor Prp8p. RNA. 2006;12:292-302 pubmed
    ..Our results define a new UBD and suggest functional links between ubiquitin and the pre-mRNA splicing machinery. ..
  8. Nottrott S, Urlaub H, Luhrmann R. Hierarchical, clustered protein interactions with U4/U6 snRNA: a biochemical role for U4/U6 proteins. EMBO J. 2002;21:5527-38 pubmed
    ..This uneven clustering of the U4/U6 snRNP-specific proteins on U4/U6 snRNA is consistent with a sequential dissociation of the U4/U6 duplex prior to spliceosome catalysis. ..
  9. Martínez Gimeno M, Gamundi M, Hernan I, Maseras M, Milla E, Ayuso C, et al. Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2003;44:2171-7 pubmed
    ..The existence of asymptomatic carriers of the nonsense mutation in the PRPF31 gene suggests incomplete penetrance for these mutations in the families. ..
  10. Stevens S, Abelson J. Purification of the yeast U4/U6.U5 small nuclear ribonucleoprotein particle and identification of its proteins. Proc Natl Acad Sci U S A. 1999;96:7226-31 pubmed
  11. Pena V, Rozov A, Fabrizio P, Luhrmann R, Wahl M. Structure and function of an RNase H domain at the heart of the spliceosome. EMBO J. 2008;27:2929-40 pubmed publisher
    ..These data suggest that Prp8 employs an RNase H domain to help assemble and stabilize the spliceosomal catalytic core, coordinate the activities of other splicing factors and possibly participate in chemical catalysis of splicing. ..
  12. Stanek D, Rader S, Klingauf M, Neugebauer K. Targeting of U4/U6 small nuclear RNP assembly factor SART3/p110 to Cajal bodies. J Cell Biol. 2003;160:505-16 pubmed
    ..We propose that U4 and U6 snRNPs accumulate in CBs for the purpose of assembly into U4/U6 snRNPs by SART3/p110...
  13. Comitato A, Spampanato C, Chakarova C, Sanges D, Bhattacharya S, Marigo V. Mutations in splicing factor PRPF3, causing retinal degeneration, form detrimental aggregates in photoreceptor cells. Hum Mol Genet. 2007;16:1699-707 pubmed
    ..Our data suggest that the mutant protein has a cell-specific dominant effect in rod photoreceptors while appears not to be harmful to epithelial and fibroblast cells. ..
  14. Schwelnus W, Richert K, Opitz F, Gross T, Habara Y, Tani T, et al. Fission yeast Prp4p kinase regulates pre-mRNA splicing by phosphorylating a non-SR-splicing factor. EMBO Rep. 2001;2:35-41 pubmed
    ..These results are consistent with the notion that Prp4p kinase is involved in the control of the formation of active spliceosomes, targeting non-SR splicing factors. ..
  15. Wagner J, Jankowsky E, Company M, Pyle A, Abelson J. The DEAH-box protein PRP22 is an ATPase that mediates ATP-dependent mRNA release from the spliceosome and unwinds RNA duplexes. EMBO J. 1998;17:2926-37 pubmed
    ..Significantly, these data suggest that the DEAH-box proteins act directly on RNA substrates within the spliceosome. ..
  16. Dellaire G, Makarov E, Cowger J, Longman D, Sutherland H, Luhrmann R, et al. Mammalian PRP4 kinase copurifies and interacts with components of both the U5 snRNP and the N-CoR deacetylase complexes. Mol Cell Biol. 2002;22:5141-56 pubmed
  17. 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
  18. Boon K, Grainger R, Ehsani P, Barrass J, Auchynnikava T, Inglehearn C, et al. prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast. Nat Struct Mol Biol. 2007;14:1077-83 pubmed
    ..We therefore propose a novel assembly pathway for U5 snRNP complexes that is disrupted by mutations that cause human RP. ..
  19. Pena V, Liu S, Bujnicki J, Luhrmann R, Wahl M. Structure of a multipartite protein-protein interaction domain in splicing factor prp8 and its link to retinitis pigmentosa. Mol Cell. 2007;25:615-24 pubmed
    ..We conclude that the expanded Prp8 Jab1/MPN domain represents a pseudoenzyme converted into a protein-protein interaction platform and that dysfunction of this platform underlies Retinitis pigmentosa. ..
  20. Ingelfinger D, Arndt Jovin D, Luhrmann R, Achsel T. The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrnl in distinct cytoplasmic foci. RNA. 2002;8:1489-501 pubmed
    ..Therefore, the foci contain a partially or fully assembled machinery for the degradation of mRNA. ..
  21. Häcker I, Sander B, Golas M, Wolf E, Karagöz E, Kastner B, et al. Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy. Nat Struct Mol Biol. 2008;15:1206-12 pubmed publisher
    ..The head and arm adopt variable relative positions. This molecular organization and dynamics suggest possible scenarios for structural events during catalytic activation. ..
  22. Bell M, Schreiner S, Damianov A, Reddy R, Bindereif A. p110, a novel human U6 snRNP protein and U4/U6 snRNP recycling factor. EMBO J. 2002;21:2724-35 pubmed
    ..In summary, p110 represents the human ortholog of Prp24, and associates only transiently with U6 and U4/U6 snRNPs during the recycling phase of the spliceosome cycle. ..
  23. Makarova O, Makarov E, Liu S, Vornlocher H, Luhrmann R. 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. 2002;21:1148-57 pubmed
    ..Thus, our studies suggest that disruptions in tri-snRNP formation and function resulting from mutations in the 61K protein may contribute to the manifestation of this disease. ..
  24. 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
    ..Hprp3p and Hprp4p have been shown to interact with each other and the first 100 amino acids of Hprp3p are not essential for this interaction. These experiments suggest that both Hprp3p and Hprp4p are components of human spliceosomes. ..
  25. 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
    ..These findings suggest that the NH(2)-terminal region of hPRP4 may play regulatory roles under an unidentified signal transduction pathway through Clk1. ..
  26. Liu S, Li P, Dybkov O, Nottrott S, Hartmuth K, Luhrmann R, et al. Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP. Science. 2007;316:115-20 pubmed
    ..Yeast two-hybrid analyses suggest a link between retinitis pigmentosa and an aberrant hPrp31-hPrp6 interaction that blocks U4/U6-U5 tri-snRNP formation. ..
  27. Mathew R, Hartmuth K, Möhlmann S, Urlaub H, Ficner R, Luhrmann R. Phosphorylation of human PRP28 by SRPK2 is required for integration of the U4/U6-U5 tri-snRNP into the spliceosome. Nat Struct Mol Biol. 2008;15:435-43 pubmed publisher
    ..Our results demonstrate a role for SRPK2 in splicing and reveal a previously unknown function for PRP28 in spliceosome assembly. ..
  28. Raghunathan P, Guthrie C. A spliceosomal recycling factor that reanneals U4 and U6 small nuclear ribonucleoprotein particles. Science. 1998;279:857-60 pubmed
    ..Addition of purified Prp24 protein regenerates duplex U4/U6 snRNPs for new rounds of splicing. The reannealing reaction catalyzed by Prp24 proceeds more efficiently with snRNPs than with deproteinized snRNAs. ..
  29. Raghunathan P, Guthrie C. RNA unwinding in U4/U6 snRNPs requires ATP hydrolysis and the DEIH-box splicing factor Brr2. Curr Biol. 1998;8:847-55 pubmed
    ..The unwinding function of Brr2 can be antagonized by the annealing activity of Prp24. We propose the existence of a dynamic cycle, uncoupled from splicing, that interconverts free and base-paired U4/U6 snRNPs. ..
  30. Brenner T, Guthrie C. Assembly of Snu114 into U5 snRNP requires Prp8 and a functional GTPase domain. RNA. 2006;12:862-71 pubmed
    ..Since Prp8 is thought to regulate the activity of the DEAD-box ATPases, this strategy of snRNP assembly could ensure that Prp8 activity is itself regulated by a GTP-dependent mechanism. ..
  31. Wada Y, Itabashi T, Sato H, Tamai M. Clinical features of a Japanese family with autosomal dominant retinitis pigmentosa associated with a Thr494Met mutation in the HPRP3 gene. Graefes Arch Clin Exp Ophthalmol. 2004;242:956-61 pubmed
    ..One patient also had retinoblastoma as a child. We conclude that the Thr494Met mutation in the HPRP3 gene causes ADRP in Japanese patients. This mutation was found in 1% of patients with ADRP in Japan. ..
  32. Makarov E, Makarova O, Achsel T, Luhrmann R. The human homologue of the yeast splicing factor prp6p contains multiple TPR elements and is stably associated with the U5 snRNP via protein-protein interactions. J Mol Biol. 2000;298:567-75 pubmed
    ..Consistent with this idea, we show that in vitro translated U5-102kD protein binds to purified 13S U4/U6 snRNPs, which contain, in addition to the Sm proteins, all known U4/U6-specific proteins. ..
  33. Ritchie D, Schellenberg M, Gesner E, Raithatha S, Stuart D, Macmillan A. Structural elucidation of a PRP8 core domain from the heart of the spliceosome. Nat Struct Mol Biol. 2008;15:1199-205 pubmed publisher
  34. Fabrizio P, Esser S, Kastner B, Luhrmann R. Isolation of S. cerevisiae snRNPs: comparison of U1 and U4/U6.U5 to their human counterparts. Science. 1994;264:261-5 pubmed
    ..U5 snRNPs are significantly similar. The preparative isolation of yeast snRNPs will allow the cloning as well as genetic and phylogenetic analysis of snRNP proteins which will accelerate our understanding of their function. ..
  35. Rader S, Guthrie C. A conserved Lsm-interaction motif in Prp24 required for efficient U4/U6 di-snRNP formation. RNA. 2002;8:1378-92 pubmed
    ..We conclude that the conserved C-terminal motif of Prp24 interacts with the Lsm proteins to promote U4/U6 formation. ..
  36. Gross T, Lützelberger M, Weigmann H, Klingenhoff A, Shenoy S, Kaufer N. Functional analysis of the fission yeast Prp4 protein kinase involved in pre-mRNA splicing and isolation of a putative mammalian homologue. Nucleic Acids Res. 1997;25:1028-35 pubmed
    ..pombe. Prp4 and the recombinant yeast/mouse protein kinase phosphorylate the human SR splicing factor ASF/SF2 in vitro in its RS domain. ..
  37. 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
    ..Based on their structural similarity with essential splicing factors in yeast, the human U4/U6-60kD and 90kD proteins are likely also to play important roles in the mammalian splicing process. ..
  38. Chakarova C, Hims M, Bolz H, Abu Safieh L, Patel R, Papaioannou M, et al. Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa. Hum Mol Genet. 2002;11:87-92 pubmed
    ..The identification of mutations in a third pre-mRNA splicing factor gene further highlights a novel mechanism of photoreceptor degeneration due to defects in the splicing process. ..
  39. Kuhn A, Brow D. Suppressors of a cold-sensitive mutation in yeast U4 RNA define five domains in the splicing factor Prp8 that influence spliceosome activation. Genetics. 2000;155:1667-82 pubmed
  40. Pannone B, Xue D, Wolin S. A role for the yeast La protein in U6 snRNP assembly: evidence that the La protein is a molecular chaperone for RNA polymerase III transcripts. EMBO J. 1998;17:7442-53 pubmed
    ..These results provide evidence that Lhp1p is a molecular chaperone for polymerase III-transcribed RNAs and implicate Lsm8p as a key component in the very early steps of U6 snRNP assembly. ..
  41. Tomasevic N, Peculis B. Xenopus LSm proteins bind U8 snoRNA via an internal evolutionarily conserved octamer sequence. Mol Cell Biol. 2002;22:4101-12 pubmed
    ..This purified complex can bind U6 snRNA in vitro but does not bind U3 or U14 snoRNA in vitro, demonstrating that the LSm complex specifically recognizes U8 RNA. ..
  42. Yang K, Zhang L, Xu T, Heroux A, Zhao R. Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins. Proc Natl Acad Sci U S A. 2008;105:13817-22 pubmed publisher
    ..These results also demonstrate an analogy between a spliceosomal protein and ribosomal proteins that insert extensions into folded rRNAs and stabilize the ribosome. ..
  43. Urushiyama S, Tani T, Ohshima Y. The prp1+ gene required for pre-mRNA splicing in Schizosaccharomyces pombe encodes a protein that contains TPR motifs and is similar to Prp6p of budding yeast. Genetics. 1997;147:101-15 pubmed
    ..These results suggest that Prp1p/Zer1p is either directly or indirectly involved in cell cycle progression and/or poly(A)+ RNA nuclear export, in addition to pre-mRNA splicing. ..
  44. Achsel T, Ahrens K, Brahms H, Teigelkamp S, Luhrmann R. The human U5-220kD protein (hPrp8) forms a stable RNA-free complex with several U5-specific proteins, including an RNA unwindase, a homologue of ribosomal elongation factor EF-2, and a novel WD-40 protein. Mol Cell Biol. 1998;18:6756-66 pubmed
    ..Since the 220kD protein is also known to contact both the pre-mRNA and the U5 snRNA, it is in a position to relay the functional state of the spliceosome to the other proteins in the complex and thus modulate their activity. ..
  45. 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
  46. 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. ..
  47. 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. ..
  48. Gottschalk A, Neubauer G, Banroques J, Mann M, Luhrmann R, Fabrizio P. Identification by mass spectrometry and functional analysis of novel proteins of the yeast [U4/U6.U5] tri-snRNP. EMBO J. 1999;18:4535-48 pubmed
    ..This suggests that these proteins, at least in part, are also present in a [U2.U4/U6.U5] tetra-snRNP complex. ..
  49. Maroney P, Romfo C, Nilsen T. Functional recognition of 5' splice site by U4/U6.U5 tri-snRNP defines a novel ATP-dependent step in early spliceosome assembly. Mol Cell. 2000;6:317-28 pubmed
    ..We propose that U1 and U5 snRNPs functionally collaborate to recognize and define the 5' splice site prior to establishment of communication with the 3' splice site. ..
  50. Potashkin J, Kim D, Fons M, Humphrey T, Frendewey D. Cell-division-cycle defects associated with fission yeast pre-mRNA splicing mutants. Curr Genet. 1998;34:153-63 pubmed
    ..These results suggest a connection between pre-mRNA splicing and the control of cell division in fission yeast. ..
  51. van Nues R, Beggs J. Functional contacts with a range of splicing proteins suggest a central role for Brr2p in the dynamic control of the order of events in spliceosomes of Saccharomyces cerevisiae. Genetics. 2001;157:1451-67 pubmed
    ..Overall, these protein interaction studies shed light on how splicing factors regulate the order of events in the large spliceosome complex. ..
  52. Maita H, Kitaura H, Ariga H, Iguchi Ariga S. Association of PAP-1 and Prp3p, the products of causative genes of dominant retinitis pigmentosa, in the tri-snRNP complex. Exp Cell Res. 2005;302:61-8 pubmed
    ..These results also suggest that splicing factors implicated in adRP contribute alone or mutually to proper splicing in the retina and that loss of their functions leads to onset of adRP. ..
  53. Brown J, Beggs J. Roles of PRP8 protein in the assembly of splicing complexes. EMBO J. 1992;11:3721-9 pubmed
  54. Patel S, Novikova N, Bellini M. Splicing-independent recruitment of spliceosomal small nuclear RNPs to nascent RNA polymerase II transcripts. J Cell Biol. 2007;178:937-49 pubmed
    ..Collectively, these data indicate that the recruitment of snRNPs to nascent transcripts and the assembly of the spliceosome are uncoupled events. ..
  55. Bellare P, Small E, Huang X, Wohlschlegel J, Staley J, Sontheimer E. A role for ubiquitin in the spliceosome assembly pathway. Nat Struct Mol Biol. 2008;15:444-51 pubmed publisher
    ..Finally, we show that the conserved splicing factor Prp8 is ubiquitinated within purified triple snRNPs. These results reveal a previously unknown ubiquitin-dependent mechanism for controlling the pre-mRNA splicing pathway. ..
  56. Galisson F, Legrain P. The biochemical defects of prp4-1 and prp6-1 yeast splicing mutants reveal that the PRP6 protein is required for the accumulation of the [U4/U6.U5] tri-snRNP. Nucleic Acids Res. 1993;21:1555-62 pubmed
    ..These results establish that the PRP6 protein is required for the accumulation of the [U4/U6.U5] tri-snRNP. We found no evidence for the presence of the PRP6 protein in the U4/U6 particle. ..
  57. Blencowe B, Carmo Fonseca M, Behrens S, Luhrmann R, Lamond A. Interaction of the human autoantigen p150 with splicing snRNPs. J Cell Sci. 1993;105 ( Pt 3):685-97 pubmed
    ..Addition of the purified U4/U6.U5 tri-snRNP restores splicing activity to inactivated HeLa nuclear extracts in which splicing had been inhibited by specific depletion of either the U4/U6 or U5 snRNPs. ..