Structural analyses of the pre-mRNA splicing machinery

Protein Science

Volumn 22, Issue 6, 2013, Pages 677-692

  Zhang, Lingdi ^a   Li, Xueni ^a   Zhao, Rui ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

Crystallography; Electron microscopy; NMR; Pre mRNA splicing; Spliceosome; Structure

Indexed keywords

DEAD BOX PROTEIN; MESSENGER RNA; MESSENGER RNA PRECURSOR; PRP8 PROTEIN; RIBONUCLEASE H; RNA HELICASE; SMALL NUCLEAR RNA; UNCLASSIFIED DRUG;

CATALYSIS; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; ELECTRON MICROSCOPY; EUKARYOTE; GENE EXPRESSION; HUMAN; INTRON; MACHINE; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN RNA BINDING; REVIEW; RNA SPLICING; RNA STRUCTURE; SPLICEOSOME; STRUCTURE ANALYSIS;

ANIMALS; HUMANS; MODELS, MOLECULAR; RIBONUCLEOPROTEINS, SMALL NUCLEAR; RNA HELICASES; RNA PRECURSORS; RNA SPLICING; RNA, SMALL NUCLEAR; RNA-BINDING PROTEINS; SPLICEOSOMES;

EID: 84881300801     PISSN: 09618368     EISSN: 1469896X     Source Type: Journal    
DOI: 10.1002/pro.2266     Document Type: Review

References (121)

1. Mattick JS, Gagen MJ (2001) The evolution of controlled multitasked gene networks: The role of introns and other noncoding RNAs in the development of complex organisms. Mol Biol Evol 18:1611-1630.
2. Nilsen TW, Graveley BR (2010) Expansion of the eukaryotic proteome by alternative splicing. Nature 463: 457-463.
3. Venables JP (2002) Alternative splicing in the testes. Curr Opin Genet Dev 12:615-619.
4. Lopez AJ (1998) Alternative splicing of pre-mRNA: developmental consequences and mechanisms of regulation. Annu Rev Genet 32:279-305.
5. Grabowski PJ, Black DL (2001) Alternative RNA splicing in the nervous system. Prog Neurobiol 65: 289-308.
6. Faustino NA, Cooper TA (2003) Pre-mRNA splicing and human disease. Genes Dev 17:419-437.
7. Philips AV, Cooper TA (2000) RNA processing and human disease. Cell Mol Life Sci 57:235-249.
8. Krawczak M, Reiss J, Cooper DN (1992) The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum Genet 90:41-54.
9. Moore MJ, Query CC, Sharp PA, Splicing of precursors to mRNA by the spliceosome. In: Gesteland R, and Atkins J, Ed.(1993) The RNA World. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 303-357.
10. Hastings ML, Krainer AR (2001) Pre-mRNA splicing in the new millennium. Curr Opin Cell Biol 13: 302-309.
11. Jurica MS, Moore MJ (2003) Pre-mRNA splicing: awash in a sea of proteins. Mol Cell 12:5-14.
12. Nilsen TW (2003) The spliceosome: The most complex macromolecular machine in the cell? Bioessays 25: 1147-1149.
13. Wahl MC, Will CL, Luhrmann R (2009) The spliceosome: design principles of a dynamic RNP machine. Cell 136:701-718.
14. Brow DA (2002) Allosteric cascade of spliceosome activation. Annu Rev Genet 36:333-360.
15. Staley JP, Guthrie C (1998) Mechanical devices of the spliceosome: motors, clocks, springs, and things. Cell 92:315-326.
16. Behzadnia N, Golas MM, Hartmuth K, Sander B, Kastner B, Deckert J, Dube P, Will CL, Urlaub H, Stark H, Leuhrmann R (2007) Composition and threedimensional EM structure of double affinity-purified, human prespliceosomal A complexes. EMBO J 26: 1737-1748.
17. Boehringer D, Makarov EM, Sander B, Makarova OV, Kastner B, Leuhrmann R, Stark H (2004) Threedimensional structure of a pre-catalytic human spliceosomal complex B. Nat Struct Mol Biol 11:463-468.
18. Jurica MS, Sousa D, Moore MJ, Grigorieff N (2004) Three-dimensional structure of C complex spliceosomes by electron microscopy. Nat Struct Mol Biol 11: 265-269.
19. Golas MM, Sander B, Bessonov S, Grote M, Wolf E, Kastner B, Stark H, Leuhrmann R (2010) 3D cryo-EM structure of an active step I spliceosome and localization of its catalytic core. Mol Cell 40:927-938.
20. Wolf E, Kastner B, Deckert J, Merz C, Stark H, Leuhrmann R (2009) Exon, intron and splice site locations in the spliceosomal B complex. EMBO J 28: 2283-2292.
21. Alcid EA, Jurica MS (2008) A protein-based EM label for RNA identifies the location of exons in spliceosomes. Nat Struct Mol Biol 15:213-215.
22. Stroupe ME, Xu C, Goode BL, Grigorieff N (2009) Actin filament labels for localizing protein components in large complexes viewed by electron microscopy. RNA 15:244-248.
23. Deckert J, Hartmuth K, Boehringer D, Behzadnia N, Will CL, Kastner B, Stark H, Urlaub H, Luhrmann R (2006) Protein composition and electron microscopy structure of affinity-purified human spliceosomal B complexes isolated under physiological conditions. Mol Cell Biol 26:5528-5543.
24. Bessonov S, Anokhina M, Krasauskas A, Golas MM, Sander B, Will CL, Urlaub H, Stark H, Leuhrmann R (2010) Characterization of purified human Bact spliceosomal complexes reveals compositional and morphological changes during spliceosome activation and first step catalysis. RNA 16:2384-2403.
25. Fabrizio P, Dannenberg J, Dube P, Kastner B, Stark H, Urlaub H, Leuhrmann R (2009) The evolutionarily conserved core design of the catalytic activation step of the yeast spliceosome. Mol Cell 36:593-608.
26. Warkocki Z, Odenwealder P, Schmitzova J, Platzmann F, Stark H, Urlaub H, Ficner R, Fabrizio P, Leuhrmann R (2009) Reconstitution of both steps of Saccharomyces cerevisiae splicing with purified spliceosomal components. Nat Struct Mol Biol 16: 1237-1243.
27. Herold N, Will CL, Wolf E, Kastner B, Urlaub H, Leuhrmann R (2009) Conservation of the protein composition and electron microscopy structure of Drosophila melanogaster and human spliceosomal complexes. Mol Cell Biol 29:281-301.
28. Stark H, Dube P, Luhrmann R, Kastner B (2001) Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle. Nature 409:539-542.
29. Pomeranz Krummel DA, Oubridge C, Leung AK, Li J, Nagai K (2009) Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution. Nature 458: 475-480.
30. Behrens SE, Tyc K, Kastner B, Reichelt J, Luhrmann R (1993) Small nuclear ribonucleoprotein (RNP) U2 contains numerous additional proteins and has a bipartite RNP structure under splicing conditions. Mol Cell Biol 13:307-319.
31. MacMillan AM, Query CC, Allerson CR, Chen S, Verdine GL, Sharp PA (1994) Dynamic association of proteins with the pre-mRNA branch region. Genes Dev 8: 3008-3020.
32. Query CC, Strobel SA, Sharp PA (1996) Three recognition events at the branch-site adenine. EMBO J 15: 1392-1402.
33. Will CL, Urlaub H, Achsel T, Gentzel M, Wilm M, Leuhrmann R (2002) Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p homologue and an SF3b DEAD-box protein. EMBO J 21:4978-4988.
34. Golas MM, Sander B, Will CL, Luhrmann R, Stark H (2003) Molecular architecture of the multiprotein splicing factor SF3b. Science 300:980-984.
35. Sander B, Golas MM, Makarov EM, Brahms H, Kastner B, Leuhrmann R, Stark H (2006) Organization of core spliceosomal components U5 snRNA loop I and U4=U6 Di-snRNP within U4=U6.U5 Tri-snRNP as revealed by electron cryomicroscopy. Mol Cell 24: 267-278.
36. Hacker I, Sander B, Golas MM, Wolf E, Karageoz E, Kastner B, Stark H, Fabrizio P, Leuhrmann R (2008) Localization of Prp8, Brr2, Snu114 and U4=U6 proteins in the yeast tri-snRNP by electron microscopy. Nat Struct Mol Biol 15:1206-1212.
37. Karaduman R, Dube P, Stark H, Fabrizio P, Kastner B, Leuhrmann R (2008) Structure of yeast U6 snRNPs: arrangement of Prp24p and the LSm complex as revealed by electron microscopy. RNA 14:2528-2537.
38. Wyatt JR, Sontheimer EJ, Steitz JA (1992) Site-specific cross-linking of mammalian U5 snRNP to the 5' splice site before the first step of pre-mRNA splicing. Genes Dev 6:2542-2553.
39. Sontheimer EJ, Steitz JA (1993) The U5 and U6 small nuclear RNAs as active site components of the spliceosome. Science 262:1989-1996.
40. McConnell TS, Steitz JA (2001) Proximity of the invariant loop of U5 snRNA to the second intron residue during pre-mRNA splicing. EMBO J 20: 3577-3586.
41. Weber G, Trowitzsch S, Kastner B, Luhrmann R, Wahl MC (2010) Functional organization of the Sm core in the crystal structure of human U1 snRNP. EMBO J 29:4172-4184.
42. Bringmann P, Luhrmann R (1986) Purification of the individual snRNPs U1, U2, U5 and U4=U6 from HeLa cells and characterization of their protein constituents. EMBO J 5:3509-3516.
43. Ruby SW, Abelson J (1988) An early hierarchic role of U1 small nuclear ribonucleoprotein in spliceosome assembly. Science 242:1028-1035.
44. Krol A, Westhof E, Bach M, Leuhrmann R, Ebel JP, Carbon P (1990) Solution structure of human U1 snRNA. Derivation of a possible three-dimensional model. Nucleic Acids Res 18:3803-3811 (1990).
45. Patton JR, Pederson T (1988) The Mr 70,000 protein of the U1 small nuclear ribonucleoprotein particle binds to the 5' stem-loop of U1 RNA and interacts with Sm domain proteins. Proc Natl Acad Sci USA 85: 747-751.
46. Bach M, Krol A, Luhrmann R (1990) Structureprobing of U1 snRNPs gradually depleted of the U1-specific proteins A, C and 70k. Evidence that A interacts differentially with developmentally regulated mouse U1 snRNA variants. Nucleic Acids Res 18:449-457.
47. Nelissen RL, Will CL, van Venrooij WJ, Luhrmann R (1994) The association of the U1-specific 70K and C proteins with U1 snRNPs is mediated in part by common U snRNP proteins. EMBO J 13:4113-4125.
48. Kambach C, Walke S, Young R, Avis JM, de la Fortelle E, Raker VA, Leuhrmann R, Li J, Nagai K (1999) Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell 96:375-387.
49. Oubridge C, Ito N, Evans PR, Teo CH, Nagai K (1994) Crystal structure at 1.92 A resolution of the RNAbinding domain of the U1A spliceosomal protein complexed with an RNA hairpin. Nature 372:432-438.
50. Muto Y, Pomeranz Krummel D, Oubridge C, Hernandez H, Robinson CV, Neuhaus D, Nagai K (2004) The structure and biochemical properties of the human spliceosomal protein U1C. J Mol Biol 341:185-198.
51. Will CL, Rumpler S, Klein Gunnewiek J, van Venrooij WJ, Luhrmann R (1996) In vitro reconstitution of mammalian U1 snRNPs active in splicing: The U1-C protein enhances the formation of early (E) spliceosomal complexes. Nucleic Acids Res 24:4614-4623.
52. Leung AK, Nagai K, Li J (2011) Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis. Nature 473:536-539.
53. Grainger RJ, Beggs JD (2005) Prp8 protein: at the heart of the spliceosome. RNA 11:533-557.
54. Li X, Zhang W, Xu T, Ramsey J, Zhang L, Hill R, Hansen KC, Hesselberth JR, Zhao R (2013) Comprehensive in vivo RNA-binding site analyses reveal a role of Prp8 in spliceosomal assembly. Nucleic Acids Res 41:3805-3518.
55. Pena V, Liu S, Bujnicki JM, Luhrmann R, Wahl MC (2007) Structure of a multipartite protein-protein interaction domain in splicing factor prp8 and its link to retinitis pigmentosa. Mol Cell 25:615-624.
56. Zhang L, Shen J, Guarnieri MT, Heroux A, Yang K, Zhao R (2007) Crystal structure of the C-terminal domain of splicing factor Prp8 carrying retinitis pigmentosa mutants. Protein Sci 16:1024-1031.
57. Yang K, Zhang L, Xu T, Heroux A, Zhao R (2008) Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins. Proc Natl Acad Sci USA 105:13817-13822.
58. Ritchie DB, Schellenberg MJ, Gesner EM, Raithatha SA, Stuart DT, Macmillan AM (2008) Structural elucidation of a PRP8 core domain from the heart of the spliceosome. Nat Struct Mol Biol 15:1199-1205.
59. Pena V, Rozov A, Fabrizio P, Luhrmann R, Wahl MC (2008) Structure and function of an RNase H domain at the heart of the spliceosome. EMBO J 27: 2929-2940.
60. Galej WP, Oubridge C, Newman AJ, Nagai K (2013) Crystal structure of Prp8 reveals active site cavity of the spliceosome. Nature 493:638-643.
61. Dlakic M, Mushegian A (2011) Prp8, the pivotal protein of the spliceosomal catalytic center, evolved from a retroelement-encoded reverse transcriptase. RNA 17:799-808.
62. Turner IA, Norman CM, Churcher MJ, Newman AJ (2006) Dissection of Prp8 protein defines multiple interactions with crucial RNA sequences in the catalytic core of the spliceosome. RNA 12:375-386.
63. Kuhn AN, Brow DA (2000) Suppressors of a cold-sensitive mutation in yeast U4 RNA define five domains in the splicing factor Prp8 that influence spliceosome activation. Genetics 155:1667-1682.
64. Kuhn AN, Reichl EM, Brow DA (2002) Distinct domains of splicing factor Prp8 mediate different aspects of spliceosome activation. Proc Natl Acad Sci USA 99:9145-9149.
65. Clery A, Blatter M, Allain FH (2008) RNA recognition motifs: boring? Not quite. Curr Opin Struct Biol 18: 290-298.
66. Sickmier EA, Frato KE, Shen H, Paranawithana SR, Green MR, Kielkopf CL (2006) Structural basis for polypyrimidine tract recognition by the essential premRNA splicing factor U2AF65. Mol Cell 23:49-59.
67. Raghunathan PL, Guthrie C (1998) A spliceosomal recycling factor that reanneals U4 and U6 small nuclear ribonucleoprotein particles. Science 279:857-860.
68. Bae E, Reiter NJ, Bingman CA, Kwan SS, Lee D, Phillips GN Jr, Butcher SE, Brow DA (2007) Structure and interactions of the first three RNA recognition motifs of splicing factor prp24. J Mol Biol 367: 1447-1458.
69. Martin-Tumasz S, Reiter NJ, Brow DA, Butcher SE (2010) Structure and functional implications of a complex containing a segment of U6 RNA bound by a domain of Prp24. RNA 16:792-804.
70. Martin-Tumasz S, Richie AC, Clos LJ 2nd, Brow DA, Butcher SE (2011) A novel occluded RNA recognition motif in Prp24 unwinds the U6 RNA internal stem loop. Nucleic Acids Res 39:7837-7847.
71. Kielkopf CL, Rodionova NA, Green MR, Burley SK (2001) A novel peptide recognition mode revealed by the X-ray structure of a core U2AF35=U2AF65 heterodimer. Cell 106:595-605.
72. Selenko P, Gregorovic G, Sprangers R, Stier G, Rhani Z, Kreamer A, Sattler M (2003) Structural basis for the molecular recognition between human splicing factors U2AF65 and SF1=mBBP. Mol Cell 11:965-976.
73. Kielkopf CL, Lucke S, Green MR (2004) U2AF homology motifs: protein recognition in the RRM world. Genes Dev 18:1513-1526.
74. Klug A, Rhodes D (1987) Zinc fingers: a novel protein fold for nucleic acid recognition. Cold Spring Harbor Symp Quant Biol 52:473-482.
75. Lin PC, Xu RM (2012) Structure and assembly of the SF3a splicing factor complex of U2 snRNP. EMBO J 31:1579-1590.
76. Liu Z, Luyten I, Bottomley MJ, Messias AC, Houngninou-Molango S, Sprangers R, Zanier K, Kreamer A, Sattler M (2001) Structural basis for recognition of the intron branch site RNA by splicing factor Science 294:1098-1102.
77. Lewis HA, Musunuru K, Jensen KB, Edo C, Chen H, Darnell RB, Burley SK (2000) Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome. Cell 100:323-332.
78. Gorbalenya AE, Koonin EV (1993) Helicases: amino acid sequence comparisons and structure-function relationships. Curr Opin Struct Biol 3:419-429.
79. Pyle AM (2011) RNA helicases and remodeling proteins. Curr Opin Chem Biol 15:636-642.
80. Jankowsky E, Fairman ME (2007) RNA helicases- one fold for many functions. Curr Opin Struct Biol 17: 316-324.
81. Cordin O, Banroques J, Tanner NK, Linder P (2006) The DEAD-box protein family of RNA helicases. Gene 367:17-37.
82. Tanner NK, Linder P (2001) DExD=H box RNA helicases: from generic motors to specific dissociation functions. Mol Cell 8:251-262 (2001).
83. Wagner JD, Jankowsky E, Company M, Pyle AM, Abelson JN (1998) The DEAH-box protein PRP22 is an ATPase that mediates ATP-dependent mRNA release from the spliceosome and unwinds RNA duplexes. EMBO J 17:2926-2937.
84. Schwer B, Gross CH (1998) Prp22, a DExH-box RNA helicase, plays two distinct roles in yeast pre-mRNA splicing. EMBO J 17:2086-2094.
85. Laggerbauer B, Achsel T, Luhrmann R (1998) The human U5-200kD DEXH-box protein unwinds U4=U6 RNA duplices in vitro. Proc Natl Acad Sci USA 95: 4188-4192.
86. Wang Y, Wagner JD, Guthrie C (1998) The DEAH-box splicing factor Prp16 unwinds RNA duplexes in vitro. Curr Biol 8:441-451.
87. Tanaka N, Schwer B (2006) Mutations in PRP43 that uncouple RNA-dependent NTPase activity and premRNA splicing function. Biochemistry 45:6510-6521.
88. Shen J, Zhang L, Zhao R (2007) Biochemical characterization of the ATPase and helicase activity of UAP56, an essential pre-mRNA splicing and mRNA export factor. J Biol Chem 282:22544-22550.
89. Jankowsky E (2011) RNA helicases at work: binding and rearranging. Trends Biochem Sci 36:19-29.
90. Yang Q, Del Campo M, Lambowitz AM, Jankowsky E (2007) DEAD-box proteins unwind duplexes by local strand separation. Mol Cell 28:253-263.
91. Jankowsky E, Gross CH, Shuman S, Pyle AM (2000) The DExH protein NPH-II is a processive and directional motor for unwinding RNA. Nature 403: 447-451.
92. Pang PS, Jankowsky E, Planet PJ, Pyle AM (2002) The hepatitis C viral NS3 protein is a processive DNA helicase with cofactor enhanced RNA unwinding. EMBO J 21:1168-1176.
93. Burgess S, Couto JR, Guthrie C (1990) A putative ATP binding protein influences the fidelity of branchpoint recognition in yeast splicing. Cell 60:705-717.
94. Burgess SM, Guthrie C (1993) A mechanism to enhance mRNA splicing fidelity: The RNA-dependent ATPase Prp16 governs usage of a discard pathway for aberrant lariat intermediates. Cell 73:1377-1391.
95. Burgess SM, Guthrie C (1993) Beat the clock: paradigms for NTPases in the maintenance of biological fidelity. Trends Biochem Sci 18:381-384.
96. Mayas RM, Maita H, Staley JP (2006) Exon ligation is proofread by the DExD=H-box ATPase Prp22p. Nat Struct Mol Biol 13:482-490.
97. Xu YZ, Query CC (2007) Competition between the ATPase Prp5 and branch region-U2 snRNA pairing modulates the fidelity of spliceosome assembly. Mol Cell 28:838-849.
98. Zhao R, Shen J, Green MR, MacMorris M, Blumenthal T (2004) Crystal structure of UAP56, a DExD=Hbox protein involved in pre-mRNA splicing and mRNA export. Structure 12:1373-1381.
99. Shi H, Cordin O, Minder CM, Linder P, Xu RM (2004) Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci USA 101:17628-17633.
100. Fleckner J, Zhang M, Valcarcel J, Green MR (1997) U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. Genes Dev 11:1864-1872.
101. Sengoku T, Nureki O, Nakamura A, Kobayashi S, Yokoyama S (2006) Structural basis for RNA unwinding by the DEAD-box protein Drosophila vasa. Cell 125:287-300.
102. Arenas JE, Abelson JN (1997) Prp43: an RNA helicase-like factor involved in spliceosome disassembly. Proc Natl Acad Sci USA 94:11798-11802.
103. Lebaron S, Papin C, Capeyrou R, Chen YL, Froment C, Monsarrat B, Caizergues-Ferrer M, Grigoriev M, Henry Y (2009) The ATPase and helicase activities of Prp43p are stimulated by the G-patch protein Pfa1p during yeast ribosome biogenesis. EMBO J 28:3808-3819.
104. Walbott H, Mouffok S, Capeyrou R, Lebaron S, Humbert O, van Tilbeurgh H, Henry Y, Leulliot N (2010) Prp43p contains a processive helicase structural architecture with a specific regulatory domain. EMBO J 29:2194-2204.
105. He Y, Andersen GR, Nielsen KH (2010) Structural basis for the function of DEAH helicases. EMBO Rep 11: 180-186.
106. Kudlinzki D, Schmitt A, Christian H, Ficner R (2012) Structural analysis of the C-terminal domain of the spliceosomal helicase Prp22. Biol Chem 393: 1131-1140.
107. Silverman EJ, Maeda A, Wei J, Smith P, Beggs JD, Lin RJ (2004) Interaction between a G-patch protein and a spliceosomal DEXD=H-box ATPase that is critical for splicing. Mol Cell Biol 24:10101-10110.
108. Raghunathan PL, Guthrie C (1998) RNA unwinding in U4=U6 snRNPs requires ATP hydrolysis and the DEIH-box splicing factor Brr2. Curr Biol 8:847-855.
109. Kim DH, Rossi JJ (1999) The first ATPase domain of the yeast 246-kDa protein is required for in vivo unwinding of the U4=U6 duplex. RNA 5:959-971.
110. Small EC, Leggett SR, Winans AA, Staley JP (2006) The EF-G-like GTPase Snu114p regulates spliceosome dynamics mediated by Brr2p, a DExD=H box ATPase. Mol Cell 23:389-399.
111. Zhang L, Xu T, Maeder C, Bud LO, Shanks J, Nix J, Guthrie C, Pleiss JA, Zhao R (2009) Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2. Nat Struct Mol Biol 16: 731-739.
112. Pena V, Jovin SM, Fabrizio P, Orlowski J, Bujnicki JM, Leuhrmann R, Wahl MC (2009) Common design principles in the spliceosomal RNA helicase Brr2 and in the Hel308 DNA helicase. Mol Cell 35:454-466.
113. Santos KF, Jovin SM, Weber G, Pena V, Leuhrmann R, Wahl MC (2012) Structural basis for functional cooperation between tandem helicase cassettes in Brr2-mediated remodeling of the spliceosome. Proc Natl Acad Sci USA 109:17418-17423.
114. Valadkhan S (2010) Role of the snRNAs in spliceosomal active site. RNA Biol 7:345-353.
115. Huppler A, Nikstad LJ, Allmann AM, Brow DA, Butcher SE (2002) Metal binding and base ionization in the U6 RNA intramolecular stem-loop structure. Nat Struct Biol 9:431-435.
116. Blad H, Reiter NJ, Abildgaard F, Markley JL, Butcher SE (2005) Dynamics and metal ion binding in the U6 RNA intramolecular stem-loop as analyzed by NMR. J Mol Biol 353:540-555.
117. Venditti V, Clos L 2nd, Niccolai N, Butcher SE (2009) Minimum-energy path for a u6 RNA conformational change involving protonation, base-pair rearrangement and base flipping. J Mol Biol 391:894-905.
118. Butcher SE, Brow DA (2005) Towards understanding the catalytic core structure of the spliceosome. Biochem Soc Trans 33:447-449.
119. Sashital DG, Cornilescu G, McManus CJ, Brow DA, Butcher SE (2004) U2-U6 RNA folding reveals a group II intron-like domain and a four-helix junction. Nat Struct Mol Biol 11:1237-1242.
120. Burke JE, Sashital DG, Zuo X, Wang YX, Butcher SE (2012) Structure of the yeast U2=U6 snRNA complex. RNA 18:673-683.
121. Hoelz A, Debler EW, Blobel G (2011) The structure of the nuclear pore complex. Annu Rev Biochem 80: 613-643.