5lqw

Structural highlights

Function

[PRP45_YEAST] Involved in pre-mRNA splicing. Associated with the spliceosome throughout the splicing reactions, until after the second catalytic step.^{[1] [2]} [RSMB_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [CWC22_YEAST] May be involved in pre-mRNA splicing. [SMD1_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Also binds telomerase RNA and is required for its accumulation.^{[3] [4]} [CEF1_YEAST] Involved in pre-mRNA splicing and cell cycle control. Required for the binding of the NTC complex (or PRP19-associated complex) components to the spliceosome to mediate conformational rearrangement or to stabilize the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation. Its absence leads to an arrest of the cell cycle, possibly due to the inefficient splicing of TUB1.^{[5] [6] [7] [8]} [SN114_YEAST] Component of the U5 snRNP complex required for pre-mRNA splicing. Binds GTP. [SMD3_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Also binds telomerase RNA and is required for its accumulation.^{[9] [10]} [PRP8_YEAST] Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U5. Has a role in branch site-3' splice site selection. Associates with the branch site-3' splice 3'-exon region. Also has a role in cell cycle.^{[11] [12] [13] [14]} [RSE1_YEAST] Involved in G2/M transition (By similarity). Required for pre-mRNA splicing and endoplasmic reticulum (ER) to Golgi secretion pathway. U2 snRNPs associated protein required for the pre-spliceosome assembly. The involvement in ER to Golgi secretion is probably indirect and due to the splicing of the pre-mRNA coding for SAR1, a small GTP-binding protein required for COPII vesicle formation from the ER.^{[15] [16]} [RUXE_YEAST] Involved in pre-mRNA splicing. Binds and is required for the stability of snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Involved in cap modification.^[17] [CLF1_YEAST] Involved in pre-mRNA splicing and cell cycle progression. Required for the spliceosome assembly by promoting the functional integration of the U4/U6.U5 tri-snRNP particle into the U1-, U2-dependent pre-spliceosome. Also recruits PRP19 to the spliceosome, as a component of the NTC complex (or PRP19-associated complex). The association of the NTC complex to the spliceosome mediates conformational rearrangement or stabilizes the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation. Required for initiation of the DNA replication by binding the RNA replication origins, probably through its interaction with the origin recognition complex (ORC).^{[18] [19] [20] [21] [22]} [PRP2_YEAST] Involved in pre-mRNA splicing. Is required together with ATP and at least one other factor, for the first cleavage-ligation reaction. Functions as a molecular motor in the activation of the precatalytic spliceosome for the first transesterification reaction of pre-mRNA splicing by hydrolyzing ATP to cause the activation of the spliceosome without the occurrence of splicing. Capable of hydrolyzing nucleoside triphosphates in the presence of single-stranded RNAs such as poly(U).^{[23] [24] [25] [26] [27]} [SMD2_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [RUXG_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [CWC2_YEAST] Involved in the first step of pre-mRNA splicing. Required for cell growth and cell cycle control. Plays a role in the levels of the U1, U4, U5 and U6 snRNAs and the maintenance of the U4/U6 snRNA complex. May provide the link between the "nineteen complex" NTC spliceosome protein complex and the spliceosome through the U6 snRNA. Associates predominantly with U6 snRNAs in assembled active spliceosomes. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Binds also to U1, U4, U5 and U6 snRNAs and to pre-mRNAs, in vitro. Is not required for the Prp2-mediated remodeling of the activated spliceosome.^{[28] [29]} [BRR2_YEAST] RNA helicase that plays an essential role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes. Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome.^{[30] [31] [32] [33]} [PRP46_YEAST] Involved in pre-mRNA splicing. May also be required for cell cycle progression at G2/M (By similarity).^[34] [PML1_YEAST] Required for efficient splicing and pre-mRNA nuclear retention.^[35] [YSF3_YEAST] Involved in pre-mRNA splicing. Required for the SF3b integrity and prespliceosome assembly.^[36] [SYF1_YEAST] Involved in pre-mRNA splicing and cell cycle control. As a component of the NTC complex (or PRP19-associated complex), associates to the spliceosome to mediate conformational rearrangement or to stabilize the structure of the spliceosome after U4 snRNA dissociation, which leads to spliceosome maturation.^{[37] [38]} [SF3B1_YEAST] Contacts pre-mRNA on both sides of the branch site early in spliceosome assembly. [IST3_YEAST] Required for pre-mRNA splicing and spliceosome assembly. As part of the pre-mRNA retention and splicing (RES) complex, required for nuclear pre-mRNA retention and efficient splicing. Required for MER1-activated splicing.^{[39] [40] [41]} [SLT11_YEAST] Involved in pre-mRNA splicing. Facilitates the cooperative formation of U2/U6 helix II in association with stem II in the spliceosome. Binds to RNA.^{[42] [43]} [RUXF_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [RDS3_YEAST] Required for pre-mRNA splicing. Involved in regulation of drug sensitivity and may play a role in multidrug resistance.^{[44] [45]} [CWC26_YEAST] Required for efficient splicing and pre-mRNA nuclear retention. May also be involved in positioning the proximal bud pole signal.^{[46] [47] [48] [49]} [BUD31_YEAST] Involved in pre-mRNA splicing. Important for bud site selection.

See Also

• Pre-mRNA splicing factors 3D structures

References

1. ↑ Martinkova K, Lebduska P, Skruzny M, Folk P, Puta F. Functional mapping of Saccharomyces cerevisiae Prp45 identifies the SNW domain as essential for viability. J Biochem. 2002 Oct;132(4):557-63. PMID:12359070
2. ↑ Albers M, Diment A, Muraru M, Russell CS, Beggs JD. Identification and characterization of Prp45p and Prp46p, essential pre-mRNA splicing factors. RNA. 2003 Jan;9(1):138-50. PMID:12554883
3. ↑ Seto AG, Zaug AJ, Sobel SG, Wolin SL, Cech TR. Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature. 1999 Sep 9;401(6749):177-80. PMID:10490028 doi:http://dx.doi.org/10.1038/43694
4. ↑ Rymond BC. Convergent transcripts of the yeast PRP38-SMD1 locus encode two essential splicing factors, including the D1 core polypeptide of small nuclear ribonucleoprotein particles. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):848-52. PMID:8430095
5. ↑ Tsai WY, Chow YT, Chen HR, Huang KT, Hong RI, Jan SP, Kuo NY, Tsao TY, Chen CH, Cheng SC. Cef1p is a component of the Prp19p-associated complex and essential for pre-mRNA splicing. J Biol Chem. 1999 Apr 2;274(14):9455-62. PMID:10092627
6. ↑ Burns CG, Ohi R, Krainer AR, Gould KL. Evidence that Myb-related CDC5 proteins are required for pre-mRNA splicing. Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13789-94. PMID:10570151
7. ↑ Burns CG, Ohi R, Mehta S, O'Toole ET, Winey M, Clark TA, Sugnet CW, Ares M Jr, Gould KL. Removal of a single alpha-tubulin gene intron suppresses cell cycle arrest phenotypes of splicing factor mutations in Saccharomyces cerevisiae. Mol Cell Biol. 2002 Feb;22(3):801-15. PMID:11784857
8. ↑ Ohi R, Feoktistova A, McCann S, Valentine V, Look AT, Lipsick JS, Gould KL. Myb-related Schizosaccharomyces pombe cdc5p is structurally and functionally conserved in eukaryotes. Mol Cell Biol. 1998 Jul;18(7):4097-108. PMID:9632794
9. ↑ Seto AG, Zaug AJ, Sobel SG, Wolin SL, Cech TR. Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature. 1999 Sep 9;401(6749):177-80. PMID:10490028 doi:http://dx.doi.org/10.1038/43694
10. ↑ Roy J, Zheng B, Rymond BC, Woolford JL Jr. Structurally related but functionally distinct yeast Sm D core small nuclear ribonucleoprotein particle proteins. Mol Cell Biol. 1995 Jan;15(1):445-55. PMID:7799953
11. ↑ Jackson SP, Lossky M, Beggs JD. Cloning of the RNA8 gene of Saccharomyces cerevisiae, detection of the RNA8 protein, and demonstration that it is essential for nuclear pre-mRNA splicing. Mol Cell Biol. 1988 Mar;8(3):1067-75. PMID:2835658
12. ↑ Abovich N, Rosbash M. Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals. Cell. 1997 May 2;89(3):403-12. PMID:9150140
13. ↑ McPheeters DS, Muhlenkamp P. Spatial organization of protein-RNA interactions in the branch site-3' splice site region during pre-mRNA splicing in yeast. Mol Cell Biol. 2003 Jun;23(12):4174-86. PMID:12773561
14. ↑ 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 Sep 16;105(37):13817-22. Epub 2008 Sep 8. PMID:18779563
15. ↑ Caspary F, Shevchenko A, Wilm M, Seraphin B. Partial purification of the yeast U2 snRNP reveals a novel yeast pre-mRNA splicing factor required for pre-spliceosome assembly. EMBO J. 1999 Jun 15;18(12):3463-74. PMID:10369685 doi:http://dx.doi.org/10.1093/emboj/18.12.3463
16. ↑ Chen EJ, Frand AR, Chitouras E, Kaiser CA. A link between secretion and pre-mRNA processing defects in Saccharomyces cerevisiae and the identification of a novel splicing gene, RSE1. Mol Cell Biol. 1998 Dec;18(12):7139-46. PMID:9819400
17. ↑ Bordonne R, Tarassov I. The yeast SME1 gene encodes the homologue of the human E core protein. Gene. 1996 Oct 17;176(1-2):111-7. PMID:8918241
18. ↑ Chung S, McLean MR, Rymond BC. Yeast ortholog of the Drosophila crooked neck protein promotes spliceosome assembly through stable U4/U6.U5 snRNP addition. RNA. 1999 Aug;5(8):1042-54. PMID:10445879
19. ↑ Ben-Yehuda S, Dix I, Russell CS, McGarvey M, Beggs JD, Kupiec M. Genetic and physical interactions between factors involved in both cell cycle progression and pre-mRNA splicing in Saccharomyces cerevisiae. Genetics. 2000 Dec;156(4):1503-17. PMID:11102353
20. ↑ Russell CS, Ben-Yehuda S, Dix I, Kupiec M, Beggs JD. Functional analyses of interacting factors involved in both pre-mRNA splicing and cell cycle progression in Saccharomyces cerevisiae. RNA. 2000 Nov;6(11):1565-72. PMID:11105756
21. ↑ Zhu W, Rainville IR, Ding M, Bolus M, Heintz NH, Pederson DS. Evidence that the pre-mRNA splicing factor Clf1p plays a role in DNA replication in Saccharomyces cerevisiae. Genetics. 2002 Apr;160(4):1319-33. PMID:11973290
22. ↑ Wang Q, Hobbs K, Lynn B, Rymond BC. The Clf1p splicing factor promotes spliceosome assembly through N-terminal tetratricopeptide repeat contacts. J Biol Chem. 2003 Mar 7;278(10):7875-83. Epub 2002 Dec 31. PMID:12509417 doi:http://dx.doi.org/10.1074/jbc.M210839200
23. ↑ Edwalds-Gilbert G, Kim DH, Silverman E, Lin RJ. Definition of a spliceosome interaction domain in yeast Prp2 ATPase. RNA. 2004 Feb;10(2):210-20. PMID:14730020
24. ↑ Kim SH, Smith J, Claude A, Lin RJ. The purified yeast pre-mRNA splicing factor PRP2 is an RNA-dependent NTPase. EMBO J. 1992 Jun;11(6):2319-26. PMID:1534753
25. ↑ King DS, Beggs JD. Interactions of PRP2 protein with pre-mRNA splicing complexes in Saccharomyces cerevisiae. Nucleic Acids Res. 1990 Nov 25;18(22):6559-64. PMID:2251118
26. ↑ Teigelkamp S, McGarvey M, Plumpton M, Beggs JD. The splicing factor PRP2, a putative RNA helicase, interacts directly with pre-mRNA. EMBO J. 1994 Feb 15;13(4):888-97. PMID:8112302
27. ↑ Kim SH, Lin RJ. Spliceosome activation by PRP2 ATPase prior to the first transesterification reaction of pre-mRNA splicing. Mol Cell Biol. 1996 Dec;16(12):6810-9. PMID:8943336
28. ↑ McGrail JC, Krause A, O'Keefe RT. The RNA binding protein Cwc2 interacts directly with the U6 snRNA to link the nineteen complex to the spliceosome during pre-mRNA splicing. Nucleic Acids Res. 2009 Jul;37(13):4205-17. Epub 2009 May 12. PMID:19435883 doi:http://dx.doi.org/gkp341
29. ↑ Rasche N, Dybkov O, Schmitzova J, Akyildiz B, Fabrizio P, Luhrmann R. Cwc2 and its human homologue RBM22 promote an active conformation of the spliceosome catalytic centre. EMBO J. 2012 Mar 21;31(6):1591-604. doi: 10.1038/emboj.2011.502. Epub 2012 Jan, 13. PMID:22246180 doi:http://dx.doi.org/10.1038/emboj.2011.502
30. ↑ Maeder C, Kutach AK, Guthrie C. ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8. Nat Struct Mol Biol. 2009 Jan;16(1):42-8. doi: 10.1038/nsmb.1535. Epub 2008 Dec, 21. PMID:19098916 doi:http://dx.doi.org/10.1038/nsmb.1535
31. ↑ Hahn D, Kudla G, Tollervey D, Beggs JD. Brr2p-mediated conformational rearrangements in the spliceosome during activation and substrate repositioning. Genes Dev. 2012 Nov 1;26(21):2408-21. doi: 10.1101/gad.199307.112. PMID:23124065 doi:http://dx.doi.org/10.1101/gad.199307.112
32. ↑ Pena V, Jovin SM, Fabrizio P, Orlowski J, Bujnicki JM, Luhrmann R, Wahl MC. Common design principles in the spliceosomal RNA helicase Brr2 and in the Hel308 DNA helicase. Mol Cell. 2009 Aug 28;35(4):454-66. PMID:19716790 doi:10.1016/j.molcel.2009.08.006
33. ↑ Zhang L, Xu T, Maeder C, Bud LO, Shanks J, Nix J, Guthrie C, Pleiss JA, Zhao R. Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2. Nat Struct Mol Biol. 2009 Jul;16(7):731-9. Epub 2009 Jun 14. PMID:19525970 doi:10.1038/nsmb.1625
34. ↑ Albers M, Diment A, Muraru M, Russell CS, Beggs JD. Identification and characterization of Prp45p and Prp46p, essential pre-mRNA splicing factors. RNA. 2003 Jan;9(1):138-50. PMID:12554883
35. ↑ Dziembowski A, Ventura AP, Rutz B, Caspary F, Faux C, Halgand F, Laprevote O, Seraphin B. Proteomic analysis identifies a new complex required for nuclear pre-mRNA retention and splicing. EMBO J. 2004 Dec 8;23(24):4847-56. Epub 2004 Nov 25. PMID:15565172 doi:http://dx.doi.org/7600482
36. ↑ Wang Q, He J, Lynn B, Rymond BC. Interactions of the yeast SF3b splicing factor. Mol Cell Biol. 2005 Dec;25(24):10745-54. PMID:16314500 doi:http://dx.doi.org/25/24/10745
37. ↑ Ben-Yehuda S, Dix I, Russell CS, McGarvey M, Beggs JD, Kupiec M. Genetic and physical interactions between factors involved in both cell cycle progression and pre-mRNA splicing in Saccharomyces cerevisiae. Genetics. 2000 Dec;156(4):1503-17. PMID:11102353
38. ↑ Russell CS, Ben-Yehuda S, Dix I, Kupiec M, Beggs JD. Functional analyses of interacting factors involved in both pre-mRNA splicing and cell cycle progression in Saccharomyces cerevisiae. RNA. 2000 Nov;6(11):1565-72. PMID:11105756
39. ↑ Gottschalk A, Bartels C, Neubauer G, Luhrmann R, Fabrizio P. A novel yeast U2 snRNP protein, Snu17p, is required for the first catalytic step of splicing and for progression of spliceosome assembly. Mol Cell Biol. 2001 May;21(9):3037-46. PMID:11287609 doi:http://dx.doi.org/10.1128/MCB.21.9.3037-3046.2001
40. ↑ Dziembowski A, Ventura AP, Rutz B, Caspary F, Faux C, Halgand F, Laprevote O, Seraphin B. Proteomic analysis identifies a new complex required for nuclear pre-mRNA retention and splicing. EMBO J. 2004 Dec 8;23(24):4847-56. Epub 2004 Nov 25. PMID:15565172 doi:http://dx.doi.org/7600482
41. ↑ Spingola M, Armisen J, Ares M Jr. Mer1p is a modular splicing factor whose function depends on the conserved U2 snRNP protein Snu17p. Nucleic Acids Res. 2004 Feb 18;32(3):1242-50. Print 2004. PMID:14973223 doi:http://dx.doi.org/10.1093/nar/gkh281
42. ↑ Xu D, Friesen JD. Splicing factor slt11p and its involvement in formation of U2/U6 helix II in activation of the yeast spliceosome. Mol Cell Biol. 2001 Feb;21(4):1011-23. PMID:11158289 doi:http://dx.doi.org/10.1128/MCB.21.4.1011-1023.2001
43. ↑ Xu D, Field DJ, Tang SJ, Moris A, Bobechko BP, Friesen JD. Synthetic lethality of yeast slt mutations with U2 small nuclear RNA mutations suggests functional interactions between U2 and U5 snRNPs that are important for both steps of pre-mRNA splicing. Mol Cell Biol. 1998 Apr;18(4):2055-66. PMID:9528778
44. ↑ Akache B, Turcotte B. New regulators of drug sensitivity in the family of yeast zinc cluster proteins. J Biol Chem. 2002 Jun 14;277(24):21254-60. Epub 2002 Apr 9. PMID:11943786 doi:http://dx.doi.org/10.1074/jbc.M202566200
45. ↑ Wang Q, Rymond BC. Rds3p is required for stable U2 snRNP recruitment to the splicing apparatus. Mol Cell Biol. 2003 Oct;23(20):7339-49. PMID:14517302
46. ↑ Zahner JE, Harkins HA, Pringle JR. Genetic analysis of the bipolar pattern of bud site selection in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1996 Apr;16(4):1857-70. PMID:8657162
47. ↑ Ni L, Snyder M. A genomic study of the bipolar bud site selection pattern in Saccharomyces cerevisiae. Mol Biol Cell. 2001 Jul;12(7):2147-70. PMID:11452010
48. ↑ Vincent K, Wang Q, Jay S, Hobbs K, Rymond BC. Genetic interactions with CLF1 identify additional pre-mRNA splicing factors and a link between activators of yeast vesicular transport and splicing. Genetics. 2003 Jul;164(3):895-907. PMID:12871902
49. ↑ Dziembowski A, Ventura AP, Rutz B, Caspary F, Faux C, Halgand F, Laprevote O, Seraphin B. Proteomic analysis identifies a new complex required for nuclear pre-mRNA retention and splicing. EMBO J. 2004 Dec 8;23(24):4847-56. Epub 2004 Nov 25. PMID:15565172 doi:http://dx.doi.org/7600482
50. ↑ Rauhut R, Fabrizio P, Dybkov O, Hartmuth K, Pena V, Chari A, Kumar V, Lee CT, Urlaub H, Kastner B, Stark H, Luhrmann R. Molecular architecture of the Saccharomyces cerevisiae activated spliceosome. Science. 2016 Aug 25. pii: aag1906. PMID:27562955 doi:http://dx.doi.org/10.1126/science.aag1906