The Spliceosome: The Ultimate RNA Chaperone and Sculptor

Trends in Biochemical Sciences

Volumn 41, Issue 1, 2016, Pages 33-45

  Papasaikas, Panagiotis ^a,b   Valcárcel, Juan ^a,b,c  

^a CENTRE FOR GENOMIC REGULATION CRG   (Spain)

^b UNIVERSITAT POMPEU FABRA   (Spain)

^c INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

CHAPERONE; MESSENGER RNA; PHOSPHATE; RNA; SCAFFOLD PROTEIN;

ALTERNATIVE RNA SPLICING; BASE PAIRING; BINDING AFFINITY; BINDING SITE; CATALYSIS; COMPLEX FORMATION; HUMAN; INTRON; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN PROTEIN INTERACTION; PROTEIN RNA BINDING; PROTEIN STRUCTURE; REVIEW; RNA SEQUENCE; SEQUENCE ANALYSIS; SPLICEOSOME; CHEMISTRY; GENETICS; METABOLISM;

HUMANS; RNA; SPLICEOSOMES;

EID: 84951857907     PISSN: 09680004     EISSN: 13624326     Source Type: Journal    
DOI: 10.1016/j.tibs.2015.11.003     Document Type: Review

References (98)

1. Wahl M.C., et al. The spliceosome: design principles of a dynamic RNP machine. Cell 2009, 136:701-718.
2. Keren H., et al. Alternative splicing and evolution: diversification, exon definition and function. Nat. Rev. Genet. 2010, 11:345-355.
3. Braunschweig U., et al. Dynamic integration of splicing within gene regulatory pathways. Cell 2013, 152:1252-1269.
4. Ward A.J., Cooper T.A. The pathobiology of splicing. J. Pathol. 2010, 220:152-163.
5. Kelemen O., et al. Function of alternative splicing. Gene 2013, 514:1-30.
6. Irimia M., et al. A highly conserved program of neuronal microexons is misregulated in autistic brains. Cell 2014, 159:1511-1523.
7. Singh R.K., Cooper T.A. Pre-mRNA splicing in disease and therapeutics. Trends Mol. Med. 2012, 18:472-482.
8. Bonnal S., et al. The spliceosome as a target of novel antitumour drugs. Nat. Rev. Drug Discov. 2012, 11:847-859.
9. Lambowitz A.M., Zimmerly S. Group II introns: mobile ribozymes that invade DNA. Cold Spring Harb. Perspect. Biol. 2011, 3:a003616.
10. Martin W., Koonin E.V. Introns and the origin of nucleus-cytosol compartmentalization. Nature 2006, 440:41-45.
11. Hang J., et al. Structural basis of pre-mRNA splicing. Science 2015, 349:1191-1198.
12. Steitz T.A., Steitz J.A. A general two-metal-ion mechanism for catalytic RNA. Proc. Natl. Acad. Sci. U.S.A. 1993, 90:6498-6502.
13. Fica S.M., et al. RNA catalyses nuclear pre-mRNA splicing. Nature 2013, 503:229-234.
14. Chen W., Moore M.J. The spliceosome: disorder and dynamics defined. Curr. Opin. Struct. Biol. 2014, 24:141-149.
15. Yan C., et al. Structure of a yeast spliceosome at 3.6-angstrom resolution. Science 2015, 349:1182-1191.
16. Madhani H.D., Guthrie C. A novel base-pairing interaction between U2 and U6 snRNAs suggests a mechanism for the catalytic activation of the spliceosome. Cell 1992, 71:803-817.
17. Wassarman D.A., Steitz J.A. Interactions of small nuclear RNA's with precursor messenger RNA during in vitro splicing. Science 1992, 257:1918-1925.
18. Fica S.M., et al. Evidence for a group II intron-like catalytic triplex in the spliceosome. Nat. Struct. Mol. Biol. 2014, 21:464-471.
19. Montemayor E.J., et al. Core structure of the U6 small nuclear ribonucleoprotein at 1.7-A resolution. Nat. Struct. Mol. Biol. 2014, 21:544-551.
20. Anokhina M., et al. RNA structure analysis of human spliceosomes reveals a compact 3D arrangement of snRNAs at the catalytic core. EMBO J. 2013, 32:2804-2818.
21. Moore M.J., Sharp P.A. Evidence for two active sites in the spliceosome provided by stereochemistry of pre-mRNA splicing. Nature 1993, 365:364-368.
22. Konarska M.M., et al. Repositioning of the reaction intermediate within the catalytic center of the spliceosome. Mol. Cell 2006, 21:543-553.
23. Liu L., et al. Opposing classes of prp8 alleles modulate the transition between the catalytic steps of pre-mRNA splicing. Nat. Struct. Mol. Biol. 2007, 14:519-526.
24. Hahn D., et al. Brr2p-mediated conformational rearrangements in the spliceosome during activation and substrate repositioning. Genes Dev. 2012, 26:2408-2421.
25. Galej W.P., et al. Crystal structure of Prp8 reveals active site cavity of the spliceosome. Nature 2013, 493:638-643.
26. Nguyen T.H., et al. The architecture of the spliceosomal U4/U6.U5 tri-snRNP. Nature 2015, 523:47-52.
27. Dlakic M., Mushegian A. Prp8, the pivotal protein of the spliceosomal catalytic center, evolved from a retroelement-encoded reverse transcriptase. RNA 2011, 17:799-808.
28. Nojima T., et al. Mammalian NET-Seq reveals genome-wide nascent transcription coupled to RNA processing. Cell 2015, 161:526-540.
29. Gornemann J., et al. Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires the cap binding complex. Mol. Cell 2005, 19:53-63.
30. Tilgner H., et al. Nucleosome positioning as a determinant of exon recognition. Nat. Struct. Mol. Biol. 2009, 16:996-1001.
31. Khodor Y.L., et al. Nascent-seq indicates widespread cotranscriptional pre-mRNA splicing in Drosophila. Genes Dev. 2011, 25:2502-2512.
32. Braberg H., et al. From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II. Cell 2013, 154:775-788.
33. de la Mata M., et al. A slow RNA polymerase II affects alternative splicing in vivo. Mol. Cell 2003, 12:525-532.
34. Lin S., et al. The splicing factor SC35 has an active role in transcriptional elongation. Nat. Struct. Mol. Biol. 2008, 15:819-826.
35. Naftelberg S., et al. Regulation of alternative splicing through coupling with transcription and chromatin structure. Annu. Rev Biochem. 2015, 84:165-198.
36. Luco R.F., et al. Epigenetics in alternative pre-mRNA splicing. Cell 2011, 144:16-26.
37. Girard C., et al. Post-transcriptional spliceosomes are retained in nuclear speckles until splicing completion. Nat. Commun. 2012, 3:994.
38. Liu Y.C., Cheng S.C. Functional roles of DExD/H-box RNA helicases in Pre-mRNA splicing. J. Biomed. Sci. 2015, 22:54.
39. Mozaffari-Jovin S., et al. The Prp8 RNase H-like domain inhibits Brr2-mediated U4/U6 snRNA unwinding by blocking Brr2 loading onto the U4 snRNA. Genes Dev. 2012, 26:2422-2434.
40. Mozaffari-Jovin S., et al. Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8. Science 2013, 341:80-84.
41. Mozaffari-Jovin S., et al. Novel regulatory principles of the spliceosomal Brr2 RNA helicase and links to retinal disease in humans. RNA Biol. 2014, 11:298-312.
42. McKie A.B., et al. Mutations in the pre-mRNA splicing factor gene PRPC8 in autosomal dominant retinitis pigmentosa (RP13). Hum. Mol. Genet. 2001, 10:1555-1562.
43. Towns K.V., et al. Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes. Hum. Mutat. 2010, 31:E1361-E1376.
44. Hsu T.Y., et al. The spliceosome is a therapeutic vulnerability in MYC-driven cancer. Nature 2015, 525:384-388.
45. Koh C.M., et al. MYC regulates the core pre-mRNA splicing machinery as an essential step in lymphomagenesis. Nature 2015, 523:96-100.
46. Oltean S., Bates D.O. Hallmarks of alternative splicing in cancer. Oncogene 2014, 33:5311-5318.
47. Roca X., Krainer A.R. Recognition of atypical 5' splice sites by shifted base-pairing to U1 snRNA. Nat. Struct. Mol. Biol. 2009, 16:176-182.
48. Mercer T.R., et al. Genome-wide discovery of human splicing branchpoints. Genome Res. 2015, 25:290-303.
49. Wang Z., Burge C.B. Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA 2008, 14:802-813.
50. Barash Y., et al. Deciphering the splicing code. Nature 2010, 465:53-59.
51. Xiong H.Y., et al. RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. Science 2015, 347:1254806.
52. Zhang Z., et al. SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell 2008, 133:585-600.
53. Matera A.G., Wang Z. A day in the life of the spliceosome. Nat. Rev. Mol. Cell Biol. 2014, 15:108-121.
54. Kondo Y., et al. Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5' splice site recognition. Elife 2015, 4:04986.
55. Roca X., et al. Widespread recognition of 5' splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides. Genes Dev. 2012, 26:1098-1109.
56. Roca X., et al. Pick one, but be quick: 5' splice sites and the problems of too many choices. Genes Dev. 2013, 27:129-144.
57. Förch P., et al. The splicing regulator TIA-1 interacts with U1-C to promote U1 snRNP recruitment to 5' splice sites. EMBO J. 2002, 21:6882-6892.
58. Wang Z., et al. iCLIP predicts the dual splicing effects of TIA-RNA interactions. PLoS Biol. 2010, 8:e1000530.
59. Yu Y., et al. Dynamic regulation of alternative splicing by silencers that modulate 5' splice site competition. Cell 2008, 135:1224-1236.
60. Staley J.P., Guthrie C. An RNA switch at the 5' splice site requires ATP and the DEAD box protein Prp28p. Mol. Cell 1999, 3:55-64.
61. Reyes J.L., et al. The C-terminal region of hPrp8 interacts with the conserved GU dinucleotide at the 5' splice site. RNA 1999, 5:167-179.
62. Pena V., et al. Structure and function of an RNase H domain at the heart of the spliceosome. EMBO J. 2008, 27:2929-2940.
63. Shen H., Green M.R. RS domains contact splicing signals and promote splicing by a common mechanism in yeast through humans. Genes Dev. 2006, 20:1755-1765.
64. Smith D.J., et al. Insights into branch nucleophile positioning and activation from an orthogonal pre-mRNA splicing system in yeast. Mol. Cell 2009, 34:333-343.
65. Gozani O., et al. Evidence that sequence-independent binding of highly conserved U2 snRNP proteins upstream of the branch site is required for assembly of spliceosomal complex A. Genes Dev. 1996, 10:233-243.
66. Corrionero A., et al. Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A. Genes Dev. 2011, 25:445-459.
67. Sickmier E.A., et al. Structural basis for polypyrimidine tract recognition by the essential pre-mRNA splicing factor U2AF65. Mol. Cell 2006, 23:49-59.
68. Mackereth C.D., et al. Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF. Nature 2011, 475:408-411.
69. Jenkins J.L., et al. U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs. Nucleic Acids Res. 2013, 41:3859-3873.
70. Thickman K.R., et al. Alternative conformations at the RNA-binding surface of the N-terminal U2AF(65) RNA recognition motif. J. Mol. Biol. 2007, 366:703-710.
71. Corsini L., et al. U2AF-homology motif interactions are required for alternative splicing regulation by SPF45. Nat. Struct. Mol. Biol. 2007, 14:620-629.
72. Perriman R.J., Ares M. Rearrangement of competing U2 RNA helices within the spliceosome promotes multiple steps in splicing. Genes Dev. 2007, 21:811-820.
73. Perriman R., Ares M. Invariant U2 snRNA nucleotides form a stem loop to recognize the intron early in splicing. Mol. Cell 2010, 38:416-427.
74. Liang W.W., Cheng S.C. A novel mechanism for Prp5 function in prespliceosome formation and proofreading the branch site sequence. Genes Dev. 2015, 29:81-93.
75. Hilliker A.K., et al. U2 toggles iteratively between the stem IIa and stem IIc conformations to promote pre-mRNA splicing. Genes Dev. 2007, 21:821-834.
76. Chathoth K.T., et al. A splicing-dependent transcriptional checkpoint associated with prespliceosome formation. Mol. Cell 2014, 53:779-790.
77. Koodathingal P., et al. The DEAH box ATPases Prp16 and Prp43 cooperate to proofread 5' splice site cleavage during pre-mRNA splicing. Mol. Cell 2010, 39:385-395.
78. Tseng C.K., et al. DEAH-box ATPase Prp16 has dual roles in remodeling of the spliceosome in catalytic steps. RNA 2011, 17:145-154.
79. Schneider M., et al. Exon definition complexes contain the tri-snRNP and can be directly converted into B-like precatalytic splicing complexes. Mol. Cell 2010, 38:223-235.
80. Hoskins A.A., Moore M.J. The spliceosome: a flexible, reversible macromolecular machine. Trends Biochem. Sci. 2012, 37:179-188.
81. Tseng C.K., Cheng S.C. Both catalytic steps of nuclear pre-mRNA splicing are reversible. Science 2008, 320:1782-1784.
82. Wahl M.C., Luhrmann R. SnapShot: spliceosome dynamics I. Cell 2015, 161. 1474-e1.
83. Wahl M.C., Luhrmann R. SnapShot: spliceosome dynamics II. Cell 2015, 162. 456-e1.
84. Abelson J., et al. Conformational dynamics of single pre-mRNA molecules during in vitro splicing. Nat. Struct. Mol. Biol. 2010, 17:504-512.
85. Hoskins A.A., et al. Ordered and dynamic assembly of single spliceosomes. Science 2011, 331:1289-1295.
86. Shcherbakova I., et al. Alternative spliceosome assembly pathways revealed by single-molecule fluorescence microscopy. Cell Rep. 2013, 5:151-165.
87. Chan S.P., et al. The Prp19p-associated complex in spliceosome activation. Science 2003, 302:279-282.
88. David C.J., et al. The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65-Prp19 complex. Genes Dev. 2011, 25:972-983.
89. Chanarat S., Strasser K. Splicing and beyond: the many faces of the Prp19 complex. Biochim. Biophys. Acta 2013, 1833:2126-2134.
90. Crispino J.D., et al. Complementation by SR proteins of pre-mRNA splicing reactions depleted of U1 snRNP. Science 1994, 265:1866-1869.
91. Korneta I., Bujnicki J.M. Intrinsic disorder in the human spliceosomal proteome. PLoS Comput. Biol. 2012, 8:e1002641.
92. Coelho Ribeiro Mde L., et al. Malleable ribonucleoprotein machine: protein intrinsic disorder in the Saccharomyces cerevisiae spliceosome. PeerJ 2013, 1:e2.
93. Clark T.A., et al. Genomewide analysis of mRNA processing in yeast using splicing-specific microarrays. Science 2002, 296:907-910.
94. Pleiss J.A., et al. Transcript specificity in yeast pre-mRNA splicing revealed by mutations in core spliceosomal components. PLoS Biol. 2007, 5:e90.
95. Park J.W., Graveley B.R. Use of RNA interference to dissect the roles of trans-acting factors in alternative pre-mRNA splicing. Methods 2005, 37:341-344.
96. Tejedor J.R., et al. Genome-wide identification of Fas/CD95 alternative splicing regulators reveals links with iron homeostasis. Mol. Cell 2015, 57:23-38.
97. Papasaikas P., et al. Functional splicing network reveals extensive regulatory potential of the core spliceosomal machinery. Mol. Cell 2015, 57:7-22.
98. Doolittle F., Gitschier J. The philosophical approach: an interview with ford doolittle. PLoS Genet. 2015, 11:e1005173.