Mechanistic insights into precursor messenger RNA splicing by the spliceosome (original) (raw)
Berget, S. M., Moore, C. & Sharp, P. A. Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. Proc. Natl Acad. Sci. USA74, 3171–3175 (1977). ArticleCASPubMedPubMed Central Google Scholar
Chow, L. T., Gelinas, R. E., Broker, T. R. & Roberts, R. J. An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNA. Cell12, 1–8 (1977). ArticleCASPubMed Google Scholar
Lerner, M. R. & Steitz, J. A. Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc. Natl Acad. Sci. USA76, 5495–5499 (1979). ArticleCASPubMedPubMed Central Google Scholar
Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L. & Steitz, J. A. Are snRNPs involved in splicing? Nature283, 220–224 (1980). ArticleCASPubMed Google Scholar
Hinterberger, M., Pettersson, I. & Steitz, J. A. Isolation of small nuclear ribonucleoproteins containing U1, U2, U4, U5, and U6 RNAs. J. Biol. Chem.258, 2604–2613 (1983). CASPubMed Google Scholar
Mount, S. M., Pettersson, I., Hinterberger, M., Karmas, A. & Steitz, J. A. The U1 small nuclear RNA-protein complex selectively binds a 5′ splice site in vitro. Cell33, 509–518 (1983). ArticleCASPubMed Google Scholar
Padgett, R. A., Mount, S. M., Steitz, J. A. & Sharp, P. A. Splicing of messenger RNA precursors is inhibited by antisera to small nuclear ribonucleoprotein. Cell35, 101–107 (1983). ArticleCASPubMed Google Scholar
Yang, V. W., Lerner, M. R., Steitz, J. A. & Flint, S. J. A small nuclear ribonucleoprotein is required for splicing of adenoviral early RNA sequences. Proc. Natl Acad. Sci. USA78, 1371–1375 (1981). ArticleCASPubMedPubMed Central Google Scholar
DiMaria, P. R., Kaltwasser, G. & Goldenberg, C. J. Partial purification and properties of a pre-mRNA splicing activity. J. Biol. Chem.260, 1096–1102 (1985). CASPubMed Google Scholar
Kramer, A., Keller, W., Appel, B. & Luhrmann, R. The 5′ terminus of the RNA moiety of U1 small nuclear ribonucleoprotein particles is required for the splicing of messenger RNA precursors. Cell38, 299–307 (1984). ArticleCASPubMed Google Scholar
Black, D. L., Chabot, B. & Steitz, J. A. U2 as well as U1 small nuclear ribonucleoproteins are involved in premessenger RNA splicing. Cell42, 737–750 (1985). ArticleCASPubMed Google Scholar
Krainer, A. R. & Maniatis, T. Multiple factors including the small nuclear ribonucleoproteins U1 and U2 are necessary for pre-mRNA splicing in vitro. Cell42, 725–736 (1985). ArticleCASPubMed Google Scholar
Berget, S. M. & Robberson, B. L. U1, U2, and U4/U6 small nuclear ribonucleoproteins are required for in vitro splicing but not polyadenylation. Cell46, 691–696 (1986). ArticleCASPubMed Google Scholar
Grabowski, P. J. & Sharp, P. A. Affinity chromatography of splicing complexes: U2, U5, and U4 + U6 small nuclear ribonucleoprotein particles in the spliceosome. Science233, 1294–1299 (1986). ArticleCASPubMed Google Scholar
Pikielny, C. W. & Rosbash, M. Specific small nuclear RNAs are associated with yeast spliceosomes. Cell45, 869–877 (1986). ArticleCASPubMed Google Scholar
Goldenberg, C. J. & Hauser, S. D. Accurate and efficient in vitro splicing of purified precursor RNAs specified by early region 2 of the adenovirus 2 genome. Nucleic Acids Res.11, 1337–1348 (1983). ArticleCASPubMedPubMed Central Google Scholar
Hernandez, N. & Keller, W. Splicing of in vitro synthesized messenger RNA precursors in HeLa cell extracts. Cell35, 89–99 (1983). ArticleCASPubMed Google Scholar
Padgett, R. A., Hardy, S. F. & Sharp, P. A. Splicing of adenovirus RNA in a cell-free transcription system. Proc. Natl Acad. Sci. USA80, 5230–5234 (1983). ArticleCASPubMedPubMed Central Google Scholar
Hardy, S. F., Grabowski, P. J., Padgett, R. A. & Sharp, P. A. Cofactor requirements of splicing of purified messenger RNA precursors. Nature308, 375–377 (1984). ArticleCASPubMed Google Scholar
Krainer, A. R., Maniatis, T., Ruskin, B. & Green, M. R. Normal and mutant human beta-globin pre-mRNAs are faithfully and efficiently spliced in vitro. Cell36, 993–1005 (1984). ArticleCASPubMed Google Scholar
Grabowski, P. J., Padgett, R. A. & Sharp, P. A. Messenger RNA splicing in vitro: an excised intervening sequence and a potential intermediate. Cell37, 415–427 (1984). ArticleCASPubMed Google Scholar
Padgett, R. A., Konarska, M. M., Grabowski, P. J., Hardy, S. F. & Sharp, P. A. Lariat RNA's as intermediates and products in the splicing of messenger RNA precursors. Science225, 898–903 (1984). ArticleCASPubMed Google Scholar
Ruskin, B., Krainer, A. R., Maniatis, T. & Green, M. R. Excision of an intact intron as a novel lariat structure during pre-mRNA splicing in vitro. Cell38, 317–331 (1984). ArticleCASPubMed Google Scholar
Sontheimer, E. J., Sun, S. & Piccirilli, J. A. Metal ion catalysis during splicing of premessenger RNA. Nature388, 801–805 (1997). ArticleCASPubMed Google Scholar
Yean, S. L., Wuenschell, G., Termini, J. & Lin, R. J. Metal-ion coordination by U6 small nuclear RNA contributes to catalysis in the spliceosome. Nature408, 881–884 (2000). ArticleCASPubMedPubMed Central Google Scholar
Keating, K. S., Toor, N., Perlman, P. S. & Pyle, A. M. A structural analysis of the group II intron active site and implications for the spliceosome. RNA16, 1–9 (2010). ArticlePubMedPubMed Central Google Scholar
Brody, E. & Abelson, J. The “spliceosome”: yeast pre-messenger RNA associates with a 40S complex in a splicing-dependent reaction. Science228, 963–967 (1985). ArticleCASPubMed Google Scholar
Grabowski, P. J., Seiler, S. R. & Sharp, P. A. A multicomponent complex is involved in the splicing of messenger RNA precursors. Cell42, 345–353 (1985). ArticleCASPubMed Google Scholar
Frendewey, D. & Keller, W. Stepwise assembly of a pre-mRNA splicing complex requires U-snRNPs and specific intron sequences. Cell42, 355–367 (1985). ArticleCASPubMed Google Scholar
Aebi, M., Hornig, H., Padgett, R. A., Reiser, J. & Weissmann, C. Sequence requirements for splicing of higher eukaryotic nuclear pre-mRNA. Cell47, 555–565 (1986). ArticleCASPubMed Google Scholar
Vijayraghavan, U. et al. Mutations in conserved intron sequences affect multiple steps in the yeast splicing pathway, particularly assembly of the spliceosome. EMBO J.5, 1683–1695 (1986). ArticleCASPubMedPubMed Central Google Scholar
Newman, A. J., Lin, R. J., Cheng, S. C. & Abelson, J. Molecular consequences of specific intron mutations on yeast mRNA splicing in vivo and in vitro. Cell42, 335–344 (1985). ArticleCASPubMed Google Scholar
Lamond, A. I., Konarska, M. M. & Sharp, P. A. A mutational analysis of spliceosome assembly: evidence for splice site collaboration during spliceosome formation. Genes Dev.1, 532–543 (1987). ArticleCASPubMed Google Scholar
Konarska, M. M. & Sharp, P. A. Electrophoretic separation of complexes involved in the splicing of precursors to mRNAs. Cell46, 845–855 (1986). ArticleCASPubMed Google Scholar
Pikielny, C. W., Rymond, B. C. & Rosbash, M. Electrophoresis of ribonucleoproteins reveals an ordered assembly pathway of yeast splicing complexes. Nature324, 341–345 (1986). ArticleCASPubMed Google Scholar
Konarska, M. M. & Sharp, P. A. Interactions between small nuclear ribonucleoprotein particles in formation of spliceosomes. Cell49, 763–774 (1987). ArticleCASPubMed Google Scholar
Bindereif, A. & Green, M. R. An ordered pathway of snRNP binding during mammalian pre-mRNA splicing complex assembly. EMBO J.6, 2415–2424 (1987). ArticleCASPubMedPubMed Central Google Scholar
Wahl, M. C., Will, C. L. & Luhrmann, R. The spliceosome: design principles of a dynamic RNP machine. Cell136, 701–718 (2009). ArticleCASPubMed Google Scholar
Bringmann, P. & Luhrmann, R. 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 (1986). ArticleCASPubMedPubMed Central Google Scholar
Lossky, M., Anderson, G. J., Jackson, S. P. & Beggs, J. Identification of a yeast snRNP protein and detection of snRNP-snRNP interactions. Cell51, 1019–1026 (1987). ArticleCASPubMed Google Scholar
Jackson, S. P., Lossky, M. & Beggs, J. D. 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.8, 1067–1075 (1988). ArticleCASPubMedPubMed Central Google Scholar
Tarn, W. Y. et al. Functional association of essential splicing factor(s) with PRP19 in a protein complex. EMBO J.13, 2421–2431 (1994). ArticleCASPubMedPubMed Central Google Scholar
Chan, S. P., Kao, D. I., Tsai, W. Y. & Cheng, S. C. The Prp19p-associated complex in spliceosome activation. Science302, 279–282 (2003). ArticleCASPubMed Google Scholar
Chabot, B. & Steitz, J. A. Multiple interactions between the splicing substrate and small nuclear ribonucleoproteins in spliceosomes. Mol. Cell. Biol.7, 281–293 (1987). ArticleCASPubMedPubMed Central Google Scholar
Parker, R., Siliciano, P. G. & Guthrie, C. Recognition of the TACTAAC box during mRNA splicing in yeast involves base pairing to the U2-like snRNA. Cell49, 229–239 (1987). ArticleCASPubMed Google Scholar
Newman, A. & Norman, C. Mutations in yeast U5 snRNA alter the specificity of 5′ splice-site cleavage. Cell65, 115–123 (1991). ArticleCASPubMed Google Scholar
Newman, A. J. & Norman, C. U5 snRNA interacts with exon sequences at 5′ and 3′ splice sites. Cell68, 743–754 (1992). ArticleCASPubMed Google Scholar
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. Cell71, 803–817 (1992). ArticleCASPubMed Google Scholar
Wassarman, D. A. & Steitz, J. A. Interactions of small nuclear RNA's with precursor messenger RNA during in vitro splicing. Science257, 1918–1925 (1992). ArticleCASPubMed Google Scholar
Wyatt, J. R., Sontheimer, E. J. & Steitz, J. A. 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 (1992). ArticleCASPubMed Google Scholar
Lesser, C. F. & Guthrie, C. Mutations in U6 snRNA that alter splice site specificity: implications for the active site. Science262, 1982–1988 (1993). ArticleCASPubMed Google Scholar
Sontheimer, E. J. & Steitz, J. A. The U5 and U6 small nuclear RNAs as active site components of the spliceosome. Science262, 1989–1996 (1993). ArticleCASPubMed Google Scholar
Kandels-Lewis, S. & Seraphin, B. Involvement of U6 snRNA in 5′ splice site selection. Science262, 2035–2039 (1993). ArticleCASPubMed Google Scholar
Newman, A. J., Teigelkamp, S. & Beggs, J. D. snRNA interactions at 5′ and 3′ splice sites monitored by photoactivated crosslinking in yeast spliceosomes. RNA1, 968–980 (1995). CASPubMedPubMed Central Google Scholar
Anokhina, M. et al. RNA structure analysis of human spliceosomes reveals a compact 3D arrangement of snRNAs at the catalytic core. EMBO J.32, 2804–2818 (2013). ArticleCASPubMedPubMed Central Google Scholar
Cordin, O., Hahn, D. & Beggs, J. D. Structure, function and regulation of spliceosomal RNA helicases. Curr. Opin. Cell Biol.24, 431–438 (2012). ArticleCASPubMed Google Scholar
Staley, J. P. & Guthrie, C. Mechanical devices of the spliceosome: motors, clocks, springs, and things. Cell92, 315–326 (1998). ArticleCASPubMed Google Scholar
Raghunathan, P. L. & Guthrie, C. RNA unwinding in U4/U6 snRNPs requires ATP hydrolysis and the DEIH-box splicing factor Brr2. Curr. Biol.8, 847–855 (1998). ArticleCASPubMed Google Scholar
Laggerbauer, B., Achsel, T. & Luhrmann, R. The human U5-200kD DEXH-box protein unwinds U4/U6 RNA duplices in vitro. Proc. Natl Acad. Sci. USA95, 4188–4192 (1998). ArticleCASPubMedPubMed Central Google Scholar
Chen, J. H. & Lin, R. J. The yeast PRP2 protein, a putative RNA-dependent ATPase, shares extensive sequence homology with two other pre-mRNA splicing factors. Nucleic Acids Res.18, 6447 (1990). ArticleCASPubMedPubMed Central Google Scholar
King, D. S. & Beggs, J. D. Interactions of PRP2 protein with pre-mRNA splicing complexes in Saccharomyces cerevisiae. Nucleic Acids Res.18, 6559–6564 (1990). ArticleCASPubMedPubMed Central Google Scholar
Kim, S. H. & Lin, R. J. Spliceosome activation by PRP2 ATPase prior to the first transesterification reaction of pre-mRNA splicing. Mol. Cell. Biol.16, 6810–6819 (1996). ArticleCASPubMedPubMed Central Google Scholar
Kim, S. H., Smith, J., Claude, A. & Lin, R. J. The purified yeast pre-mRNA splicing factor PRP2 is an RNA-dependent NTPase. EMBO J.11, 2319–2326 (1992). ArticleCASPubMedPubMed Central Google Scholar
Burgess, S., Couto, J. R. & Guthrie, C. A putative ATP binding protein influences the fidelity of branchpoint recognition in yeast splicing. Cell60, 705–717 (1990). ArticleCASPubMed Google Scholar
Schwer, B. & Guthrie, C. PRP16 is an RNA-dependent ATPase that interacts transiently with the spliceosome. Nature349, 494–499 (1991). ArticleCASPubMed Google Scholar
Company, M., Arenas, J. & Abelson, J. Requirement of the RNA helicase-like protein PRP22 for release of messenger RNA from spliceosomes. Nature349, 487–493 (1991). ArticleCASPubMed Google Scholar
Semlow, D. R., Blanco, M. R., Walter, N. G. & Staley, J. P. Spliceosomal DEAH-box ATPases remodel pre-mRNA to activate alternative splice sites. Cell164, 985–998 (2016). ArticleCASPubMedPubMed Central Google Scholar
Weber, G., Trowitzsch, S., Kastner, B., Luhrmann, R. & Wahl, M. C. Functional organization of the Sm core in the crystal structure of human U1 snRNP. EMBO J.29, 4172–4184 (2010). ArticleCASPubMedPubMed Central Google Scholar
Pomeranz Krummel, D. A., Oubridge, C., Leung, A. K., Li, J. & Nagai, K. Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution. Nature458, 475–480 (2009). ArticleCASPubMedPubMed Central Google Scholar
Kondo, Y., Oubridge, C., van Roon, A. M. & Nagai, K. Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5′ splice site recognition. Elifehttp://dx.doi.org/10.7554/eLife.04986 (2015).
Price, S. R., Evans, P. R. & Nagai, K. Crystal structure of the spliceosomal U2B”-U2A' protein complex bound to a fragment of U2 small nuclear RNA. Nature394, 645–650 (1998). ArticleCASPubMed Google Scholar
Sickmier, E. A. et al. Structural basis for polypyrimidine tract recognition by the essential pre-mRNA splicing factor U2AF65. Mol. Cell23, 49–59 (2006). ArticleCASPubMedPubMed Central Google Scholar
Jenkins, J. L., Agrawal, A. A., Gupta, A., Green, M. R. & Kielkopf, C. L. U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs. Nucleic Acids Res.41, 3859–3873 (2013). ArticleCASPubMedPubMed Central Google Scholar
Yoshida, H. et al. A novel 3′ splice site recognition by the two zinc fingers in the U2AF small subunit. Genes Dev.29, 1649–1660 (2015). ArticleCASPubMedPubMed Central Google Scholar
Leung, A. K., Nagai, K. & Li, J. Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis. Nature473, 536–539 (2011). ArticleCASPubMedPubMed Central Google Scholar
Zhou, L. et al. Crystal structures of the Lsm complex bound to the 3′ end sequence of U6 small nuclear RNA. Nature506, 116–120 (2014). ArticleCASPubMed Google Scholar
Montemayor, E. J. et al. Core structure of the U6 small nuclear ribonucleoprotein at 1.7-A resolution. Nat. Struct. Mol. Biol.21, 544–551 (2014). ArticleCASPubMedPubMed Central Google Scholar
Galej, W. P., Oubridge, C., Newman, A. J. & Nagai, K. Crystal structure of Prp8 reveals active site cavity of the spliceosome. Nature493, 638–643 (2013). ArticleCASPubMedPubMed Central Google Scholar
Mozaffari-Jovin, S. et al. Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8. Science341, 80–84 (2013). ArticleCASPubMed Google Scholar
Nguyen, T. H. et al. Structural basis of Brr2–Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site. Structure21, 910–919 (2013). ArticleCASPubMedPubMed Central Google Scholar
Cretu, C. et al. Molecular architecture of SF3b and structural consequences of its cancer-related mutations. Mol. Cell64, 307–319 (2016). ArticleCASPubMed Google Scholar
Zhou, Z., Sim, J., Griffith, J. & Reed, R. Purification and electron microscopic visualization of functional human spliceosomes. Proc. Natl Acad. Sci. USA99, 12203–12207 (2002). ArticleCASPubMedPubMed Central Google Scholar
Jurica, M. S., Licklider, L. J., Gygi, S. R., Grigorieff, N. & Moore, M. J. Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. RNA8, 426–439 (2002). ArticleCASPubMedPubMed Central Google Scholar
Luhrmann, R. & Stark, H. Structural mapping of spliceosomes by electron microscopy. Curr. Opin. Struct. Biol.19, 96–102 (2009). ArticleCASPubMed Google Scholar
Behzadnia, N. et al. Composition and three-dimensional EM structure of double affinity-purified, human prespliceosomal A complexes. EMBO J.26, 1737–1748 (2007). ArticleCASPubMedPubMed Central Google Scholar
Furman, E. & Glitz, D. G. Purification of the spliceosome A-complex and its visualization by electron microscopy. J. Biol. Chem.270, 15515–15522 (1995). ArticleCASPubMed Google Scholar
Boehringer, D. et al. Three-dimensional structure of a pre-catalytic human spliceosomal complex B. Nat. Struct. Mol. Biol.11, 463–468 (2004). ArticleCASPubMed Google Scholar
Deckert, J. et al. Protein composition and electron microscopy structure of affinity-purified human spliceosomal B complexes isolated under physiological conditions. Mol. Cell. Biol.26, 5528–5543 (2006). ArticleCASPubMedPubMed Central Google Scholar
Bessonov, S. et al. Characterization of purified human Bact spliceosomal complexes reveals compositional and morphological changes during spliceosome activation and first step catalysis. RNA16, 2384–2403 (2010). ArticleCASPubMedPubMed Central Google Scholar
Golas, M. M. et al. 3D cryo-EM structure of an active step I spliceosome and localization of its catalytic core. Mol. Cell40, 927–938 (2010). ArticleCASPubMed Google Scholar
Jurica, M. S., Sousa, D., Moore, M. J. & Grigorieff, N. Three-dimensional structure of C complex spliceosomes by electron microscopy. Nat. Struct. Mol. Biol.11, 265–269 (2004). ArticleCASPubMed Google Scholar
Ilagan, J. O., Chalkley, R. J., Burlingame, A. L. & Jurica, M. S. Rearrangements within human spliceosomes captured after exon ligation. RNA19, 400–412 (2013). ArticleCASPubMedPubMed Central Google Scholar
Fabrizio, P. et al. The evolutionarily conserved core design of the catalytic activation step of the yeast spliceosome. Mol. Cell36, 593–608 (2009). ArticleCASPubMed Google Scholar
Ohi, M. D., Ren, L., Wall, J. S., Gould, K. L. & Walz, T. Structural characterization of the fission yeast U5. U2/U6 spliceosome complex. Proc. Natl Acad. Sci. USA104, 3195–3200 (2007). ArticleCASPubMedPubMed Central Google Scholar
Yan, C. et al. Structure of a yeast spliceosome at 3.6-angstrom resolution. Science349, 1182–1191 (2015). ArticleCASPubMed Google Scholar
Hang, J., Wan, R., Yan, C. & Shi, Y. Structural basis of pre-mRNA splicing. Science349, 1191–1198 (2015). ArticleCASPubMed Google Scholar
Wan, R. et al. The 3.8 A structure of the U4/U6. U5 tri-snRNP: insights into spliceosome assembly and catalysis. Science351, 466–475 (2016). ArticleCASPubMed Google Scholar
Agafonov, D. E. et al. Molecular architecture of the human U4/U6. U5 tri-snRNP. Science351, 1416–1420 (2016). ArticleCASPubMed Google Scholar
Yan, C., Wan, R., Bai, R., Huang, G. & Shi, Y. Structure of a yeast activated spliceosome at 3.5 A resolution. Science353, 904–911 (2016). ArticleCASPubMed Google Scholar
Wan, R., Yan, C., Bai, R., Huang, G. & Shi, Y. Structure of a yeast catalytic step I spliceosome at 3.4 A resolution. Science353, 895–904 (2016). ArticleCASPubMed Google Scholar
Yan, C., Wan, R., Bai, R., Huang, G. & Shi, Y. Structure of a yeast step II catalytically activated spliceosome. Science355, 149–155 (2017). ArticleCASPubMed Google Scholar
Rauhut, R. et al. Molecular architecture of the Saccharomyces cerevisiae activated spliceosome. Science353, 1399–1405 (2016). ArticleCASPubMed Google Scholar
Bertram, K. et al. Cryo-EM structure of a human spliceosome activated for step 2 of splicing. Nature542, 318–323 (2017). ArticleCASPubMed Google Scholar
Fica, S. M., Mefford, M. A., Piccirilli, J. A. & Staley, J. P. Evidence for a group II intron-like catalytic triplex in the spliceosome. Nat. Struct. Mol. Biol.21, 464–471 (2014). ArticleCASPubMedPubMed Central Google Scholar
Robart, A. R., Chan, R. T., Peters, J. K., Rajashankar, K. R. & Toor, N. Crystal structure of a eukaryotic group II intron lariat. Nature514, 193–197 (2014). ArticleCASPubMedPubMed Central Google Scholar
Turner, I. A., Norman, C. M., Churcher, M. J. & Newman, A. J. Dissection of Prp8 protein defines multiple interactions with crucial RNA sequences in the catalytic core of the spliceosome. RNA12, 375–386 (2006). ArticleCASPubMedPubMed Central Google Scholar
Galej, W. P., Nguyen, T. H., Newman, A. J. & Nagai, K. Structural studies of the spliceosome: zooming into the heart of the machine. Curr. Opin. Struct. Biol.25, 57–66 (2014). ArticleCASPubMedPubMed Central Google Scholar
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. USA105, 13817–13822 (2008). ArticleCASPubMedPubMed Central Google Scholar
Rasche, N. et al. Cwc2 and its human homologue RBM22 promote an active conformation of the spliceosome catalytic centre. EMBO J.31, 1591–1604 (2012). ArticleCASPubMedPubMed Central Google Scholar
Hahn, C. N. & Scott, H. S. Spliceosome mutations in hematopoietic malignancies. Nat. Genet.44, 9–10 (2012). ArticleCAS Google Scholar
Darman, R. B. et al. Cancer-associated SF3B1 hotspot mutations induce cryptic 3′ splice site selection through use of a different branch point. Cell Rep.13, 1033–1045 (2015). ArticleCASPubMed Google Scholar
Alsafadi, S. et al. Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage. Nat. Commun.7, 10615 (2016). ArticleCASPubMedPubMed Central Google Scholar
Jacquier, A. & Michel, F. Base-pairing interactions involving the 5′ and 3′-terminal nucleotides of group II self-splicing introns. J. Mol. Biol.213, 437–447 (1990). ArticleCASPubMed Google Scholar
Chanfreau, G. & Jacquier, A. Catalytic site components common to both splicing steps of a group II intron. Science266, 1383–1387 (1994). ArticleCASPubMed Google Scholar
Luukkonen, B. G. & Seraphin, B. The role of branchpoint-3′ splice site spacing and interaction between intron terminal nucleotides in 3′ splice site selection in Saccharomyces cerevisiae. EMBO J.16, 779–792 (1997). ArticleCASPubMedPubMed Central Google Scholar
Collins, C. A. & Guthrie, C. Genetic interactions between the 5′ and 3′ splice site consensus sequences and U6 snRNA during the second catalytic step of pre-mRNA splicing. RNA7, 1845–1854 (2001). CASPubMedPubMed Central Google Scholar
Frank, D. & Guthrie, C. An essential splicing factor, SLU7, mediates 3′ splice site choice in yeast. Genes Dev.6, 2112–2124 (1992). ArticleCASPubMed Google Scholar
Umen, J. G. & Guthrie, C. Prp16p, Slu7p, and Prp8p interact with the 3′ splice site in two distinct stages during the second catalytic step of pre-mRNA splicing. RNA1, 584–597 (1995). CASPubMedPubMed Central Google Scholar
Umen, J. G. & Guthrie, C. Mutagenesis of the yeast gene PRP8 reveals domains governing the specificity and fidelity of 3′ splice site selection. Genetics143, 723–739 (1996). CASPubMedPubMed Central Google Scholar
Chua, K. & Reed, R. The RNA splicing factor hSlu7 is required for correct 3′ splice-site choice. Nature402, 207–210 (1999). ArticleCASPubMed Google Scholar
Chen, W. & Moore, M. J. The spliceosome: disorder and dynamics defined. Curr. Opin. Struct. Biol.24, 141–149 (2014). ArticleCASPubMed Google Scholar
Ohrt, T. et al. Prp2-mediated protein rearrangements at the catalytic core of the spliceosome as revealed by dcFCCS. RNA18, 1244–1256 (2012). ArticleCASPubMedPubMed Central Google Scholar
Grainger, R. J., Barrass, J. D., Jacquier, A., Rain, J. C. & Beggs, J. D. Physical and genetic interactions of yeast Cwc21p, an ortholog of human SRm300/SRRM2, suggest a role at the catalytic center of the spliceosome. RNA15, 2161–2173 (2009). ArticleCASPubMedPubMed Central Google Scholar
Warkocki, Z. et al. Reconstitution of both steps of Saccharomyces cerevisiae splicing with purified spliceosomal components. Nat. Struct. Mol. Biol.16, 1237–1243 (2009). ArticleCASPubMed Google Scholar
Chiu, Y. F. et al. Cwc25 is a novel splicing factor required after Prp2 and Yju2 to facilitate the first catalytic reaction. Mol. Cell. Biol.29, 5671–5678 (2009). ArticleCASPubMedPubMed Central Google Scholar
Krishnan, R. et al. Biased Brownian ratcheting leads to pre-mRNA remodeling and capture prior to first-step splicing. Nat. Struct. Mol. Biol.20, 1450–1457 (2013). ArticleCASPubMedPubMed Central Google Scholar
Ohrt, T. et al. Molecular dissection of step 2 catalysis of yeast pre-mRNA splicing investigated in a purified system. RNA19, 902–915 (2013). ArticleCASPubMedPubMed Central Google Scholar
James, S. A., Turner, W. & Schwer, B. How Slu7 and Prp18 cooperate in the second step of yeast pre-mRNA splicing. RNA8, 1068–1077 (2002). ArticleCASPubMedPubMed Central Google Scholar
Zhang, X. & Schwer, B. Functional and physical interaction between the yeast splicing factors Slu7 and Prp18. Nucleic Acids Res.25, 2146–2152 (1997). ArticleCASPubMedPubMed Central Google Scholar
Santos, K. F. et al. Structural basis for functional cooperation between tandem helicase cassettes in Brr2-mediated remodeling of the spliceosome. Proc. Natl Acad. Sci. USA109, 17418–17423 (2012). ArticleCASPubMedPubMed Central Google Scholar
Hahn, D., Kudla, G., Tollervey, D. & Beggs, J. D. Brr2p-mediated conformational rearrangements in the spliceosome during activation and substrate repositioning. Genes Dev.26, 2408–2421 (2012). ArticleCASPubMedPubMed Central Google Scholar
Huang, Y. H., Chung, C. S., Kao, D. I., Kao, T. C. & Cheng, S. C. Sad1 counteracts Brr2-mediated dissociation of U4/U6. U5 in tri-snRNP homeostasis. Mol. Cell. Biol.34, 210–220 (2014). ArticleCASPubMedPubMed Central Google Scholar
McPheeters, D. S. & 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.23, 4174–4186 (2003). ArticleCASPubMedPubMed Central Google Scholar
Schneider, C. et al. Dynamic contacts of U2, RES, Cwc25, Prp8 and Prp45 proteins with the pre-mRNA branch-site and 3′ splice site during catalytic activation and step 1 catalysis in yeast spliceosomes. PLoS Genet.11, e1005539 (2015). ArticleCASPubMedPubMed Central Google Scholar
Edwalds-Gilbert, G., Kim, D. H., Silverman, E. & Lin, R. J. Definition of a spliceosome interaction domain in yeast Prp2 ATPase. RNA10, 210–220 (2004). ArticleCASPubMedPubMed Central Google Scholar
Liu, H. L. & Cheng, S. C. The interaction of Prp2 with a defined region of the intron is required for the first splicing reaction. Mol. Cell. Biol.32, 5056–5066 (2012). ArticleCASPubMedPubMed Central Google Scholar
Warkocki, Z. et al. The G-patch protein Spp2 couples the spliceosome-stimulated ATPase activity of the DEAH-box protein Prp2 to catalytic activation of the spliceosome. Genes Dev.29, 94–107 (2015). ArticleCASPubMedPubMed Central Google Scholar
Teigelkamp, S., McGarvey, M., Plumpton, M. & Beggs, J. D. The splicing factor PRP2, a putative RNA helicase, interacts directly with pre-mRNA. EMBO J.13, 888–897 (1994). ArticleCASPubMedPubMed Central Google Scholar
Lardelli, R. M., Thompson, J. X., Yates, J. R. 3rd & Stevens, S. W. Release of SF3 from the intron branchpoint activates the first step of pre-mRNA splicing. RNA16, 516–528 (2010). ArticlePubMedPubMed Central Google Scholar
Schwer, B. & Guthrie, C. A conformational rearrangement in the spliceosome is dependent on PRP16 and ATP hydrolysis. EMBO J.11, 5033–5039 (1992). ArticleCASPubMedPubMed Central Google Scholar
Tseng, C. K., Liu, H. L. & Cheng, S. C. DEAH-box ATPase Prp16 has dual roles in remodeling of the spliceosome in catalytic steps. RNA17, 145–154 (2011). ArticleCASPubMedPubMed Central Google Scholar
Schwer, B. A conformational rearrangement in the spliceosome sets the stage for Prp22-dependent mRNA release. Mol. Cell30, 743–754 (2008). ArticleCASPubMedPubMed Central Google Scholar
Schwer, B. & Gross, C. H. Prp22, a DExH-box RNA helicase, plays two distinct roles in yeast pre-mRNA splicing. EMBO J.17, 2086–2094 (1998). ArticleCASPubMedPubMed Central Google Scholar
Cech, T. R. The generality of self-splicing RNA: relationship to nuclear mRNA splicing. Cell44, 207–210 (1986). ArticleCASPubMed Google Scholar
Maroney, P. A., Romfo, C. M. & Nilsen, T. W. Functional recognition of 5′ splice site by U4/U6. U5 tri-snRNP defines a novel ATP-dependent step in early spliceosome assembly. Mol. Cell6, 317–328 (2000). ArticleCASPubMed Google Scholar
Tsai, R. T. et al. Spliceosome disassembly catalyzed by Prp43 and its associated components Ntr1 and Ntr2. Genes Dev.19, 2991–3003 (2005). ArticleCASPubMedPubMed Central Google Scholar
Fourmann, J. B., Tauchert, M. J., Ficner, R., Fabrizio, P. & Luhrmann, R. Regulation of Prp43-mediated disassembly of spliceosomes by its cofactors Ntr1 and Ntr2. Nucleic Acids Res.45, 4068–4080 (2017). ArticleCASPubMed Google Scholar