DOI: 10.1038/nature14548. The architecture of the spliceosomal U4/U6.U5 tri-snRNP

The architecture of the spliceosomal U4/U6.U5 tri-snRNP

10.1038/nature14548

Crossref journal-article

Springer Science and Business Media LLC

Nature (297)

Bibliography

Nguyen, T. H. D., Galej, W. P., Bai, X., Savva, C. G., Newman, A. J., Scheres, S. H. W., & Nagai, K. (2015). The architecture of the spliceosomal U4/U6.U5 tri-snRNP. Nature, 523(7558), 47â52.

Authors 7

Thi Hoang Duong Nguyen (first)
Wojciech P. Galej (additional)
Xiao-chen Bai (additional)
Christos G. Savva (additional)
Andrew J. Newman (additional)
Sjors H. W. Scheres (additional)
Kiyoshi Nagai (additional)

References 75 Referenced 211

Will, C. L. & Lührmann, R. Spliceosome structure and function. Cold Spring Harb. Perspect. Biol. 3, a003707 (2011) / Cold Spring Harb. Perspect. Biol. by CL Will (2011)
Chan, S. P. & Cheng, S. C. The Prp19-associated complex is required for specifying interactions of U5 and U6 with pre-mRNA during spliceosome activation. J. Biol. Chem. 280, 31190–31199 (2005) (10.1074/jbc.M505060200) / J. Biol. Chem. by SP Chan (2005)
Fabrizio, P. et al. The evolutionarily conserved core design of the catalytic activation step of the yeast spliceosome. Mol. Cell 36, 593–608 (2009) (10.1016/j.molcel.2009.09.040) / Mol. Cell by P Fabrizio (2009)
Fica, S. M. et al. RNA catalyses nuclear pre-mRNA splicing. Nature 503, 229–234 (2013) (10.1038/nature12734) / Nature by SM Fica (2013)
Newman, A. J. & Norman, C. U5 snRNA interacts with exon sequences at 5′ and 3′ splice sites. Cell 68, 743–754 (1992) (10.1016/0092-8674(92)90149-7) / Cell by AJ Newman (1992)
Sontheimer, E. J. & Steitz, J. A. The U5 and U6 small nuclear RNAs as active site components of the spliceosome. Science 262, 1989–1996 (1993) (10.1126/science.8266094) / Science by EJ Sontheimer (1993)
Stevens, S. W. et al. Biochemical and genetic analyses of the U5, U6, and U4/U6.U5 small nuclear ribonucleoproteins from Saccharomyces cerevisiae. RNA 7, 1543–1553 (2001) / RNA by SW Stevens (2001)
Gottschalk, A. et al. Identification by mass spectrometry and functional analysis of novel proteins of the yeast [U4/U6.U5] tri-snRNP. EMBO J. 18, 4535–4548 (1999) (10.1093/emboj/18.16.4535) / EMBO J. by A Gottschalk (1999)
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. RNA 12, 375–386 (2006) (10.1261/rna.2229706) / RNA by IA Turner (2006)
Galej, W. P., Oubridge, C., Newman, A. J. & Nagai, K. Crystal structure of Prp8 reveals active site cavity of the spliceosome. Nature 493, 638–643 (2013) (10.1038/nature11843) / Nature by WP Galej (2013)
Fabrizio. P., Laggerbauer, B., Lauber, J., Lane, W. S. & Lührmann, R. An evolutionarily conserved U5 snRNP-specific protein is a GTP-binding factor closely related to the ribosomal translocase EF-2. EMBO J. 16, 4092–4106 (1997) (10.1093/emboj/16.13.4092) / EMBO J. by P Fabrizio (1997)
Small, E. C., Leggett, S. R., Winans, A. A. & Staley, J. P. The EF-G-like GTPase Snu114p regulates spliceosome dynamics mediated by Brr2p, a DExD/H box ATPase. Mol. Cell 23, 389–399 (2006) (10.1016/j.molcel.2006.05.043) / Mol. Cell by EC Small (2006)
Bartels. C., Urlaub, H., Lührmann, R. & Fabrizio P. Mutagenesis suggests several roles of Snu114p in pre-mRNA splicing. J. Biol. Chem. 278, 28324–28334 (2003) (10.1074/jbc.M303043200) / J. Biol. Chem. by C Bartels (2003)
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) (10.1016/S0960-9822(07)00345-4) / Curr. Biol. by PL Raghunathan (1998)
Laggerbauer, B., Achsel, T. & Lührmann, R. The human U5–200kD DEXH-box protein unwinds U4/U6 RNA duplices in vitro. Proc. Natl Acad. Sci. USA 95, 4188–4192 (1998) (10.1073/pnas.95.8.4188) / Proc. Natl Acad. Sci. USA by B Laggerbauer (1998)
Liu, S., Rauhut, R., Vornlocher, H. P. & Lührmann, R. The network of protein-protein interactions within the human U4/U6.U5 tri-snRNP. RNA 12, 1418–1430 (2006) (10.1261/rna.55406) / RNA by S Liu (2006)
van Nues, R. W. & Beggs, J. D. 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 157, 1451–1467 (2001) (10.1093/genetics/157.4.1451) / Genetics by RW van Nues (2001)
Sander, B. et al. 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 (2006) (10.1016/j.molcel.2006.08.021) / Mol. Cell by B Sander (2006)
Häcker, I. et al. Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy. Nature Struct. Mol. Biol. 15, 1206–1212 (2008) (10.1038/nsmb.1506) / Nature Struct. Mol. Biol. by I Häcker (2008)
McMullan, G. et al. Experimental observation of the improvement in MTF from backthinning a CMOS direct electron detector. Ultramicroscopy 109, 1144–1147 (2009) (10.1016/j.ultramic.2009.05.005) / Ultramicroscopy by G McMullan (2009)
Li, X. et al. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nature Methods 10, 584–590 (2013) (10.1038/nmeth.2472) / Nature Methods by X Li (2013)
Scheres, S. H. A Bayesian view on cryo-EM structure determination. J. Mol. Biol. 415, 406–418 (2012) (10.1016/j.jmb.2011.11.010) / J. Mol. Biol. by SH Scheres (2012)
Bai, X. C., McMullan, G. & Scheres, S. H. How cryo-EM is revolutionizing structural biology. Trends Biochem. Sci. 40, 49–57 (2015) (10.1016/j.tibs.2014.10.005) / Trends Biochem. Sci. by XC Bai (2015)
Scheres, S. H. Beam-induced motion correction for sub-megadalton cryo-EM particles. Elife 3, e03665 (2014) (10.7554/eLife.03665) / Elife by SH Scheres (2014)
Scheres, S. H. & Chen, S. Prevention of overfitting in cryo-EM structure determination. Nature Methods 9, 853–854 (2012) (10.1038/nmeth.2115) / Nature Methods by SH Scheres (2012)
Jørgensen, R. et al. Two crystal structures demonstrate large conformational changes in the eukaryotic ribosomal translocase. Nature Struct. Biol. 10, 379–385 (2003) (10.1038/nsb923) / Nature Struct. Biol. by R Jørgensen (2003)
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. RNA 15, 2161–2173 (2009) (10.1261/rna.1908309) / RNA by RJ Grainger (2009)
Dix, I., Russell, C. S., O'Keefe, R. T., Newman, A. J. & Beggs, J. D. Protein-RNA interactions in the U5 snRNP of Saccharomyces cerevisiae. RNA 4, 1675–1686 (1998) / RNA by I Dix (1998)
Reuter, K., Nottrott, S., Fabrizio, P., Lührmann, R. & Ficner, R. Identification, characterization and crystal structure analysis of the human spliceosomal U5 snRNP-specific 15 kD protein. J. Mol. Biol. 294, 515–525 (1999) (10.1006/jmbi.1999.3258) / J. Mol. Biol. by K Reuter (1999)
Maeder, C., Kutach, A. K. & Guthrie, C. ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8. Nature Struct. Mol. Biol. 16, 42–48 (2009) (10.1038/nsmb.1535) / Nature Struct. Mol. Biol. by C Maeder (2009)
Nguyen, T. H. D. et al. Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site. Structure 21, 910–919 (2013) (10.1016/j.str.2013.04.017) / Structure by THD Nguyen (2013)
Mozaffari-Jovin, S. et al. Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8. Science 341, 80–84 (2013) (10.1126/science.1237515) / Science by S Mozaffari-Jovin (2013)
Liu, S. et al. Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP. Science 316, 115–120 (2007) (10.1126/science.1137924) / Science by S Liu (2007)
Schultz, A., Nottrott, S., Hartmuth, K. & Lührmann, R. RNA structural requirements for the association of the spliceosomal hPrp31 protein with the U4 and U4atac small nuclear ribonucleoproteins. J. Biol. Chem. 281, 28278–28286 (2006) (10.1074/jbc.M603350200) / J. Biol. Chem. by A Schultz (2006)
Ayadi, L. et al. Functional and structural characterization of the Prp3 binding domain of the yeast Prp4 splicing factor. J. Mol. Biol. 284, 673–687 (1998) (10.1006/jmbi.1998.2183) / J. Mol. Biol. by L Ayadi (1998)
Korneta, I., Magnus, M. & Bujnicki, J. M. Structural bioinformatics of the human spliceosomal proteome. Nucleic Acids Res. 40, 7046–7065 (2012) (10.1093/nar/gks347) / Nucleic Acids Res. by I Korneta (2012)
Nottrott, S., Urlaub, H. & Lührmann, R. Hierarchical, clustered protein interactions with U4/U6 snRNA: a biochemical role for U4/U6 proteins. EMBO J. 21, 5527–5538 (2002) (10.1093/emboj/cdf544) / EMBO J. by S Nottrott (2002)
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. 21, 1555–1562 (1993) (10.1093/nar/21.7.1555) / Nucleic Acids Res. by F Galisson (1993)
Makarov, E. M., Makarova, O. V., Achsel, T. & Lührmann, 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. 298, 567–575 (2000) (10.1006/jmbi.2000.3685) / J. Mol. Biol. by EM Makarov (2000)
Boon, K. L. et al. Prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast. Nature Struct. Mol. Biol. 14, 1077–1083 (2007) (10.1038/nsmb1303) / Nature Struct. Mol. Biol. by KL Boon (2007)
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. 26, 2422–2434 (2012) (10.1101/gad.200949.112) / Genes Dev. by S Mozaffari-Jovin (2012)
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) (10.1101/gad.199307.112) / Genes Dev. by D Hahn (2012)
Büttner, K., Nehring, S. & Hofner, K. P. Structural basis for DNA duplex separation by a superfamily‐2 helicase. Nature Struct. Mol. Biol. 14, 647–652 (2007) (10.1038/nsmb1246) / Nature Struct. Mol. Biol. by K Büttner (2007)
Tourigny, D. S., Fernández, I. S., Kelley, A. C. & Ramakrishnan, V. Elongation factor G bound to the ribosome in an intermediate state of translocation. Science 340, 1235490 (2013) (10.1126/science.1235490) / Science by DS Tourigny (2013)
Lin. J, Gagnon, M. G., Bulkley, D. & Steitz, T. A. Conformational changes of elongation factor G on the ribosome during tRNA translocation. Cell 160, 219–227 (2015) (10.1016/j.cell.2014.11.049) / Cell by Lin. J (2015)
Kuhn, A. N. & Brow, D. A. 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 (2000) (10.1093/genetics/155.4.1667) / Genetics by AN Kuhn (2000)
Li, Z. & Brow, D. A. A spontaneous duplication in U6 spliceosomal RNA uncouples the early and late functions of the ACAGA element in vivo. RNA 2, 879–894 (1996) / RNA by Z Li (1996)
Toor, N., Keating, K. S., Taylor, S. D. & Pyle, A. M. Crystal structure of a self-spliced group II intron. Science 320, 77–82 (2008) (10.1126/science.1153803) / Science by N Toor (2008)
Fica, S. M., Mefford, M. A., Piccirilli, J. A. & Staley, J. P. Evidence for a group II intron-like catalytic triplex in the spliceosome. Nature Struct. Mol. Biol. 21, 464–471 (2013) (10.1038/nsmb.2815) / Nature Struct. Mol. Biol. by SM Fica (2013)
Sharp, P. A. Five easy pieces. Science 254, 663 (1991) (10.1126/science.1948046) / Science by PA Sharp (1991)
Schreieck, A. et al. RNA polymerase II termination involves C-terminal domain tyrosine dephosphorylation by CPF subunit Glc7. Nature Struct. Mol. Biol. 21, 175–179 (2014) (10.1038/nsmb.2753) / Nature Struct. Mol. Biol. by A Schreieck (2014)
Mindell, J. A. & Grigorieff, N. Accurate determination of local defocus and specimen tilt in electron microscopy. J. Struct. Biol. 142, 334–347 (2003) (10.1016/S1047-8477(03)00069-8) / J. Struct. Biol. by JA Mindell (2003)
Elmlund, H., Elmlund, D. & Bengio, S. PRIME: probabilistic initial 3D model generation for single-particle cryo-electron microscopy. Structure 21, 1299–1306 (2013) (10.1016/j.str.2013.07.002) / Structure by H Elmlund (2013)
Kucukelbir, A., Sigworth, F. J. & Tagare, H. D. Quantifying the local resolution of cryo-EM density maps. Nature Methods 11, 63–65 (2014) (10.1038/nmeth.2727) / Nature Methods by A Kucukelbir (2014)
Chen, S. et al. High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135, 24–35 (2013) (10.1016/j.ultramic.2013.06.004) / Ultramicroscopy by S Chen (2013)
Scheres, S. H. W., Nuñez-Ramirez, R., Sorzano, C. O. S., Carazo, J. M. & Marabini, R. Image processing for electron microscopy single-particle analysis using Xmipp. Nature Protocols 3, 977–990 (2008) (10.1038/nprot.2008.62) / Nature Protocols by SHW Scheres (2008)
Tang, G. et al. EMAN2: an extensive image processing suite for electron microscopy. J. Struct. Biol. 157, 38–46 (2007) (10.1016/j.jsb.2006.05.009) / J. Struct. Biol. by G Tang (2007)
Goddard, T. D., Huang, C. C. & Ferrin, T. E. Visualizing density maps with UCSF Chimera. J. Struct. Biol. 157, 281–287 (2007) (10.1016/j.jsb.2006.06.010) / J. Struct. Biol. by TD Goddard (2007)
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010) (10.1107/S0907444910007493) / Acta Crystallogr. D by P Emsley (2010)
Zhang, Y. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics 9, 40 (2008) (10.1186/1471-2105-9-40) / BMC Bioinformatics by Y Zhang (2008)
Malmström, L. et al. Superfamily assignments for the yeast proteome through integration of structure prediction with the gene ontology. PLoS Biol. 5, e76 (2007) (10.1371/journal.pbio.0050076) / PLoS Biol. by L Malmström (2007)
Wu, X. H., Chen, R. C., Gao, Y. & Wu, Y. D. The effect of Asp-His-Ser/Thr-Trp tetrad on the thermostability of WD40-repeat proteins. Biochemistry 49, 10237–10245 (2010) (10.1021/bi101321y) / Biochemistry by XH Wu (2010)
Rother, M. et al. ModeRNA server: an online tool for modeling RNA 3D structures. Bioinformatics 27, 2441–2442 (2011) (10.1093/bioinformatics/btr400) / Bioinformatics by M Rother (2011)
Dobbyn, H. C. et al. Analysis of pre-mRNA and pre-rRNA processing factor Snu13p structure and mutants. Biochem. Biophys. Res. Commun. 360, 857–862 (2007) (10.1016/j.bbrc.2007.06.163) / Biochem. Biophys. Res. Commun. by HC Dobbyn (2007)
Leung, A. K., Nagai, K. & Li, J. Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis. Nature 473, 536–539 (2011) (10.1038/nature09956) / Nature by AK Leung (2011)
Chanfreau, G., Elela, S. A., Ares, M., Jr & Guthrie, C. Alternative 3′-end processing of U5 snRNA by RNase III. Genes Dev. 11, 2741–2751 (1997) (10.1101/gad.11.20.2741) / Genes Dev. by G Chanfreau (1997)
Zhou, L. et al. Crystal structures of the Lsm complex bound to the 3′end sequence of U6 small nuclear RNA. Nature 506, 116–120 (2014) (10.1038/nature12803) / Nature by L Zhou (2014)
Query, C. C. & Konarska, M. M. Suppression of multiple substrate mutations by spliceosomal prp8 alleles suggests functional correlations with ribosomal ambiguity mutants. Mol. Cell 14, 343–354 (2004) (10.1016/S1097-2765(04)00217-5) / Mol. Cell by CC Query (2004)
Umen, J. G. & Guthrie, C. Mutagenesis of the yeast gene PRP8 reveals domains governing the specificity and fidelity of 3′ splice site selection. Genetics 143, 723–739 (1996) (10.1093/genetics/143.2.723) / Genetics by JG Umen (1996)
Liu, L., Query, C. C. & Konarska, M. M. Opposing classes of prp8 alleles modulate the transition between the catalytic steps of pre-mRNA splicing. Nature Struct. Mol. Biol. 14, 519–526 (2007) (10.1038/nsmb1240) / Nature Struct. Mol. Biol. by L Liu (2007)
Dagher, S. F. & Fu, X. D. Evidence for a role of Sky1p-mediated phosphorylation in 3′ splice site recognition involving both Prp8 and Prp17/Slu4. RNA 7, 1284–1297 (2001) (10.1017/S1355838201016077) / RNA by SF Dagher (2001)
Ben-Yehuda, S. et al. Extensive genetic interactions between PRP8 and PRP17/CDC40, two yeast genes involved in pre-mRNA splicing and cell cycle progression. Genetics 154, 61–71 (2000) (10.1093/genetics/154.1.61) / Genetics by S Ben-Yehuda (2000)
Collins, C. A. & Guthrie, C. Allele-specific genetic interactions between Prp8 and RNA active site residues suggest a function for Prp8 at the catalytic core of the spliceosome. Genes Dev. 13, 1970–1982 (1999) (10.1101/gad.13.15.1970) / Genes Dev. by CA Collins (1999)
Siatecka, M., Reyes, J. L. & Konarska, M. M. Functional interactions of Prp8 with both splice sites at the spliceosomal catalytic center. Genes Dev. 13, 1983–1993 (1999) (10.1101/gad.13.15.1983) / Genes Dev. by M Siatecka (1999)
Kuhn, A. N., Li, Z. & Brow, D. A. Splicing factor Prp8 governs U4/U6 RNA unwinding during activation of the spliceosome. Mol. Cell 3, 65–75 (1999) (10.1016/S1097-2765(00)80175-6) / Mol. Cell by AN Kuhn (1999)

Dates

Type	When
Created	10 years, 1 month ago (June 24, 2015, 4:22 p.m.)
Deposited	2 years, 3 months ago (May 18, 2023, 2:32 p.m.)
Indexed	4 weeks, 1 day ago (July 23, 2025, 8:21 a.m.)
Issued	10 years, 1 month ago (June 24, 2015)
Published	10 years, 1 month ago (June 24, 2015)
Published Online	10 years, 1 month ago (June 24, 2015)
Published Print	10 years, 1 month ago (July 1, 2015)

Funders 0

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BibTeX

@article{Nguyen_2015, title={The architecture of the spliceosomal U4/U6.U5 tri-snRNP}, volume={523}, ISSN={1476-4687}, url={http://dx.doi.org/10.1038/nature14548}, DOI={10.1038/nature14548}, number={7558}, journal={Nature}, publisher={Springer Science and Business Media LLC}, author={Nguyen, Thi Hoang Duong and Galej, Wojciech P. and Bai, Xiao-chen and Savva, Christos G. and Newman, Andrew J. and Scheres, Sjors H. W. and Nagai, Kiyoshi}, year={2015}, month=jun, pages={47–52} }

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      "volume": "68",
      "author": "AJ Newman",
      "year": "1992",
      "unstructured": "Newman, A. J. & Norman, C. U5 snRNA interacts with exon sequences at 5\u2032 and 3\u2032 splice sites. Cell 68, 743\u2013754 (1992)",
      "journal-title": "Cell"
    },
    {
      "key": "BFnature14548_CR6",
      "doi-asserted-by": "crossref",
      "first-page": "1989",
      "DOI": "10.1126/science.8266094",
      "volume": "262",
      "author": "EJ Sontheimer",
      "year": "1993",
      "unstructured": "Sontheimer, E. J. & Steitz, J. A. The U5 and U6 small nuclear RNAs as active site components of the spliceosome. Science 262, 1989\u20131996 (1993)",
      "journal-title": "Science"
    },
    {
      "key": "BFnature14548_CR7",
      "first-page": "1543",
      "volume": "7",
      "author": "SW Stevens",
      "year": "2001",
      "unstructured": "Stevens, S. W. et al. Biochemical and genetic analyses of the U5, U6, and U4/U6.U5 small nuclear ribonucleoproteins from Saccharomyces cerevisiae. RNA 7, 1543\u20131553 (2001)",
      "journal-title": "RNA"
    },
    {
      "key": "BFnature14548_CR8",
      "doi-asserted-by": "crossref",
      "first-page": "4535",
      "DOI": "10.1093/emboj/18.16.4535",
      "volume": "18",
      "author": "A Gottschalk",
      "year": "1999",
      "unstructured": "Gottschalk, A. et al. Identification by mass spectrometry and functional analysis of novel proteins of the yeast [U4/U6.U5] tri-snRNP. EMBO J. 18, 4535\u20134548 (1999)",
      "journal-title": "EMBO J."
    },
    {
      "key": "BFnature14548_CR9",
      "doi-asserted-by": "crossref",
      "first-page": "375",
      "DOI": "10.1261/rna.2229706",
      "volume": "12",
      "author": "IA Turner",
      "year": "2006",
      "unstructured": "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. RNA 12, 375\u2013386 (2006)",
      "journal-title": "RNA"
    },
    {
      "key": "BFnature14548_CR10",
      "doi-asserted-by": "crossref",
      "first-page": "638",
      "DOI": "10.1038/nature11843",
      "volume": "493",
      "author": "WP Galej",
      "year": "2013",
      "unstructured": "Galej, W. P., Oubridge, C., Newman, A. J. & Nagai, K. Crystal structure of Prp8 reveals active site cavity of the spliceosome. Nature 493, 638\u2013643 (2013)",
      "journal-title": "Nature"
    },
    {
      "key": "BFnature14548_CR11",
      "doi-asserted-by": "crossref",
      "first-page": "4092",
      "DOI": "10.1093/emboj/16.13.4092",
      "volume": "16",
      "author": "P Fabrizio",
      "year": "1997",
      "unstructured": "Fabrizio. P., Laggerbauer, B., Lauber, J., Lane, W. S. & L\u00fchrmann, R. An evolutionarily conserved U5 snRNP-specific protein is a GTP-binding factor closely related to the ribosomal translocase EF-2. EMBO J. 16, 4092\u20134106 (1997)",
      "journal-title": "EMBO J."
    },
    {
      "key": "BFnature14548_CR12",
      "doi-asserted-by": "crossref",
      "first-page": "389",
      "DOI": "10.1016/j.molcel.2006.05.043",
      "volume": "23",
      "author": "EC Small",
      "year": "2006",
      "unstructured": "Small, E. C., Leggett, S. R., Winans, A. A. & Staley, J. P. The EF-G-like GTPase Snu114p regulates spliceosome dynamics mediated by Brr2p, a DExD/H box ATPase. Mol. Cell 23, 389\u2013399 (2006)",
      "journal-title": "Mol. Cell"
    },
    {
      "key": "BFnature14548_CR13",
      "doi-asserted-by": "crossref",
      "first-page": "28324",
      "DOI": "10.1074/jbc.M303043200",
      "volume": "278",
      "author": "C Bartels",
      "year": "2003",
      "unstructured": "Bartels. C., Urlaub, H., L\u00fchrmann, R. & Fabrizio P. Mutagenesis suggests several roles of Snu114p in pre-mRNA splicing. J. Biol. Chem. 278, 28324\u201328334 (2003)",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "BFnature14548_CR14",
      "doi-asserted-by": "crossref",
      "first-page": "847",
      "DOI": "10.1016/S0960-9822(07)00345-4",
      "volume": "8",
      "author": "PL Raghunathan",
      "year": "1998",
      "unstructured": "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\u2013855 (1998)",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "BFnature14548_CR15",
      "doi-asserted-by": "crossref",
      "first-page": "4188",
      "DOI": "10.1073/pnas.95.8.4188",
      "volume": "95",
      "author": "B Laggerbauer",
      "year": "1998",
      "unstructured": "Laggerbauer, B., Achsel, T. & L\u00fchrmann, R. The human U5\u2013200kD DEXH-box protein unwinds U4/U6 RNA duplices in vitro. Proc. Natl Acad. Sci. USA 95, 4188\u20134192 (1998)",
      "journal-title": "Proc. Natl Acad. Sci. USA"
    },
    {
      "key": "BFnature14548_CR16",
      "doi-asserted-by": "crossref",
      "first-page": "1418",
      "DOI": "10.1261/rna.55406",
      "volume": "12",
      "author": "S Liu",
      "year": "2006",
      "unstructured": "Liu, S., Rauhut, R., Vornlocher, H. P. & L\u00fchrmann, R. The network of protein-protein interactions within the human U4/U6.U5 tri-snRNP. RNA 12, 1418\u20131430 (2006)",
      "journal-title": "RNA"
    },
    {
      "key": "BFnature14548_CR17",
      "doi-asserted-by": "crossref",
      "first-page": "1451",
      "DOI": "10.1093/genetics/157.4.1451",
      "volume": "157",
      "author": "RW van Nues",
      "year": "2001",
      "unstructured": "van Nues, R. W. & Beggs, J. D. 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 157, 1451\u20131467 (2001)",
      "journal-title": "Genetics"
    },
    {
      "key": "BFnature14548_CR18",
      "doi-asserted-by": "crossref",
      "first-page": "267",
      "DOI": "10.1016/j.molcel.2006.08.021",
      "volume": "24",
      "author": "B Sander",
      "year": "2006",
      "unstructured": "Sander, B. et al. 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\u2013278 (2006)",
      "journal-title": "Mol. Cell"
    },
    {
      "key": "BFnature14548_CR19",
      "doi-asserted-by": "crossref",
      "first-page": "1206",
      "DOI": "10.1038/nsmb.1506",
      "volume": "15",
      "author": "I H\u00e4cker",
      "year": "2008",
      "unstructured": "H\u00e4cker, I. et al. Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy. Nature Struct. Mol. Biol. 15, 1206\u20131212 (2008)",
      "journal-title": "Nature Struct. Mol. Biol."
    },
    {
      "key": "BFnature14548_CR20",
      "doi-asserted-by": "crossref",
      "first-page": "1144",
      "DOI": "10.1016/j.ultramic.2009.05.005",
      "volume": "109",
      "author": "G McMullan",
      "year": "2009",
      "unstructured": "McMullan, G. et al. Experimental observation of the improvement in MTF from backthinning a CMOS direct electron detector. Ultramicroscopy 109, 1144\u20131147 (2009)",
      "journal-title": "Ultramicroscopy"
    },
    {
      "key": "BFnature14548_CR21",
      "doi-asserted-by": "crossref",
      "first-page": "584",
      "DOI": "10.1038/nmeth.2472",
      "volume": "10",
      "author": "X Li",
      "year": "2013",
      "unstructured": "Li, X. et al. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nature Methods 10, 584\u2013590 (2013)",
      "journal-title": "Nature Methods"
    },
    {
      "key": "BFnature14548_CR22",
      "doi-asserted-by": "crossref",
      "first-page": "406",
      "DOI": "10.1016/j.jmb.2011.11.010",
      "volume": "415",
      "author": "SH Scheres",
      "year": "2012",
      "unstructured": "Scheres, S. H. A Bayesian view on cryo-EM structure determination. J. Mol. Biol. 415, 406\u2013418 (2012)",
      "journal-title": "J. Mol. Biol."
    },
    {
      "key": "BFnature14548_CR23",
      "doi-asserted-by": "crossref",
      "first-page": "49",
      "DOI": "10.1016/j.tibs.2014.10.005",
      "volume": "40",
      "author": "XC Bai",
      "year": "2015",
      "unstructured": "Bai, X. C., McMullan, G. & Scheres, S. H. How cryo-EM is revolutionizing structural biology. Trends Biochem. Sci. 40, 49\u201357 (2015)",
      "journal-title": "Trends Biochem. Sci."
    },
    {
      "key": "BFnature14548_CR24",
      "doi-asserted-by": "crossref",
      "first-page": "e03665",
      "DOI": "10.7554/eLife.03665",
      "volume": "3",
      "author": "SH Scheres",
      "year": "2014",
      "unstructured": "Scheres, S. H. Beam-induced motion correction for sub-megadalton cryo-EM particles. Elife 3, e03665 (2014)",
      "journal-title": "Elife"
    },
    {
      "key": "BFnature14548_CR25",
      "doi-asserted-by": "crossref",
      "first-page": "853",
      "DOI": "10.1038/nmeth.2115",
      "volume": "9",
      "author": "SH Scheres",
      "year": "2012",
      "unstructured": "Scheres, S. H. & Chen, S. Prevention of overfitting in cryo-EM structure determination. Nature Methods 9, 853\u2013854 (2012)",
      "journal-title": "Nature Methods"
    },
    {
      "key": "BFnature14548_CR26",
      "doi-asserted-by": "crossref",
      "first-page": "379",
      "DOI": "10.1038/nsb923",
      "volume": "10",
      "author": "R J\u00f8rgensen",
      "year": "2003",
      "unstructured": "J\u00f8rgensen, R. et al. Two crystal structures demonstrate large conformational changes in the eukaryotic ribosomal translocase. Nature Struct. Biol. 10, 379\u2013385 (2003)",
      "journal-title": "Nature Struct. Biol."
    },
    {
      "key": "BFnature14548_CR27",
      "doi-asserted-by": "crossref",
      "first-page": "2161",
      "DOI": "10.1261/rna.1908309",
      "volume": "15",
      "author": "RJ Grainger",
      "year": "2009",
      "unstructured": "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. RNA 15, 2161\u20132173 (2009)",
      "journal-title": "RNA"
    },
    {
      "key": "BFnature14548_CR28",
      "first-page": "1675",
      "volume": "4",
      "author": "I Dix",
      "year": "1998",
      "unstructured": "Dix, I., Russell, C. S., O'Keefe, R. T., Newman, A. J. & Beggs, J. D. Protein-RNA interactions in the U5 snRNP of Saccharomyces cerevisiae. RNA 4, 1675\u20131686 (1998)",
      "journal-title": "RNA"
    },
    {
      "key": "BFnature14548_CR29",
      "doi-asserted-by": "crossref",
      "first-page": "515",
      "DOI": "10.1006/jmbi.1999.3258",
      "volume": "294",
      "author": "K Reuter",
      "year": "1999",
      "unstructured": "Reuter, K., Nottrott, S., Fabrizio, P., L\u00fchrmann, R. & Ficner, R. Identification, characterization and crystal structure analysis of the human spliceosomal U5 snRNP-specific 15 kD protein. J. Mol. Biol. 294, 515\u2013525 (1999)",
      "journal-title": "J. Mol. Biol."
    },
    {
      "key": "BFnature14548_CR30",
      "doi-asserted-by": "crossref",
      "first-page": "42",
      "DOI": "10.1038/nsmb.1535",
      "volume": "16",
      "author": "C Maeder",
      "year": "2009",
      "unstructured": "Maeder, C., Kutach, A. K. & Guthrie, C. ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8. Nature Struct. Mol. Biol. 16, 42\u201348 (2009)",
      "journal-title": "Nature Struct. Mol. Biol."
    },
    {
      "key": "BFnature14548_CR31",
      "doi-asserted-by": "crossref",
      "first-page": "910",
      "DOI": "10.1016/j.str.2013.04.017",
      "volume": "21",
      "author": "THD Nguyen",
      "year": "2013",
      "unstructured": "Nguyen, T. H. D. et al. Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site. Structure 21, 910\u2013919 (2013)",
      "journal-title": "Structure"
    },
    {
      "key": "BFnature14548_CR32",
      "doi-asserted-by": "crossref",
      "first-page": "80",
      "DOI": "10.1126/science.1237515",
      "volume": "341",
      "author": "S Mozaffari-Jovin",
      "year": "2013",
      "unstructured": "Mozaffari-Jovin, S. et al. Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8. Science 341, 80\u201384 (2013)",
      "journal-title": "Science"
    },
    {
      "key": "BFnature14548_CR33",
      "doi-asserted-by": "crossref",
      "first-page": "115",
      "DOI": "10.1126/science.1137924",
      "volume": "316",
      "author": "S Liu",
      "year": "2007",
      "unstructured": "Liu, S. et al. Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP. Science 316, 115\u2013120 (2007)",
      "journal-title": "Science"
    },
    {
      "key": "BFnature14548_CR34",
      "doi-asserted-by": "crossref",
      "first-page": "28278",
      "DOI": "10.1074/jbc.M603350200",
      "volume": "281",
      "author": "A Schultz",
      "year": "2006",
      "unstructured": "Schultz, A., Nottrott, S., Hartmuth, K. & L\u00fchrmann, R. RNA structural requirements for the association of the spliceosomal hPrp31 protein with the U4 and U4atac small nuclear ribonucleoproteins. J. Biol. Chem. 281, 28278\u201328286 (2006)",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "BFnature14548_CR35",
      "doi-asserted-by": "crossref",
      "first-page": "673",
      "DOI": "10.1006/jmbi.1998.2183",
      "volume": "284",
      "author": "L Ayadi",
      "year": "1998",
      "unstructured": "Ayadi, L. et al. Functional and structural characterization of the Prp3 binding domain of the yeast Prp4 splicing factor. J. Mol. Biol. 284, 673\u2013687 (1998)",
      "journal-title": "J. Mol. Biol."
    },
    {
      "key": "BFnature14548_CR36",
      "doi-asserted-by": "crossref",
      "first-page": "7046",
      "DOI": "10.1093/nar/gks347",
      "volume": "40",
      "author": "I Korneta",
      "year": "2012",
      "unstructured": "Korneta, I., Magnus, M. & Bujnicki, J. M. Structural bioinformatics of the human spliceosomal proteome. Nucleic Acids Res. 40, 7046\u20137065 (2012)",
      "journal-title": "Nucleic Acids Res."
    },
    {
      "key": "BFnature14548_CR37",
      "doi-asserted-by": "crossref",
      "first-page": "5527",
      "DOI": "10.1093/emboj/cdf544",
      "volume": "21",
      "author": "S Nottrott",
      "year": "2002",
      "unstructured": "Nottrott, S., Urlaub, H. & L\u00fchrmann, R. Hierarchical, clustered protein interactions with U4/U6 snRNA: a biochemical role for U4/U6 proteins. EMBO J. 21, 5527\u20135538 (2002)",
      "journal-title": "EMBO J."
    },
    {
      "key": "BFnature14548_CR38",
      "doi-asserted-by": "crossref",
      "first-page": "1555",
      "DOI": "10.1093/nar/21.7.1555",
      "volume": "21",
      "author": "F Galisson",
      "year": "1993",
      "unstructured": "Galisson, F. & Legrain, P. The biochemical defects of prp4\u20131 and prp6\u20131 yeast splicing mutants reveal that the PRP6 protein is required for the accumulation of the [U4/U6.U5] tri-snRNP. Nucleic Acids Res. 21, 1555\u20131562 (1993)",
      "journal-title": "Nucleic Acids Res."
    },
    {
      "key": "BFnature14548_CR39",
      "doi-asserted-by": "crossref",
      "first-page": "567",
      "DOI": "10.1006/jmbi.2000.3685",
      "volume": "298",
      "author": "EM Makarov",
      "year": "2000",
      "unstructured": "Makarov, E. M., Makarova, O. V., Achsel, T. & L\u00fchrmann, 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. 298, 567\u2013575 (2000)",
      "journal-title": "J. Mol. Biol."
    },
    {
      "key": "BFnature14548_CR40",
      "doi-asserted-by": "crossref",
      "first-page": "1077",
      "DOI": "10.1038/nsmb1303",
      "volume": "14",
      "author": "KL Boon",
      "year": "2007",
      "unstructured": "Boon, K. L. et al. Prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast. Nature Struct. Mol. Biol. 14, 1077\u20131083 (2007)",
      "journal-title": "Nature Struct. Mol. Biol."
    },
    {
      "key": "BFnature14548_CR41",
      "doi-asserted-by": "crossref",
      "first-page": "2422",
      "DOI": "10.1101/gad.200949.112",
      "volume": "26",
      "author": "S Mozaffari-Jovin",
      "year": "2012",
      "unstructured": "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. 26, 2422\u20132434 (2012)",
      "journal-title": "Genes Dev."
    },
    {
      "key": "BFnature14548_CR42",
      "doi-asserted-by": "crossref",
      "first-page": "2408",
      "DOI": "10.1101/gad.199307.112",
      "volume": "26",
      "author": "D Hahn",
      "year": "2012",
      "unstructured": "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\u20132421 (2012)",
      "journal-title": "Genes Dev."
    },
    {
      "key": "BFnature14548_CR43",
      "doi-asserted-by": "crossref",
      "first-page": "647",
      "DOI": "10.1038/nsmb1246",
      "volume": "14",
      "author": "K B\u00fcttner",
      "year": "2007",
      "unstructured": "B\u00fcttner, K., Nehring, S. & Hofner, K. P. Structural basis for DNA duplex separation by a superfamily\u20102 helicase. Nature Struct. Mol. Biol. 14, 647\u2013652 (2007)",
      "journal-title": "Nature Struct. Mol. Biol."
    },
    {
      "key": "BFnature14548_CR44",
      "doi-asserted-by": "crossref",
      "first-page": "1235490",
      "DOI": "10.1126/science.1235490",
      "volume": "340",
      "author": "DS Tourigny",
      "year": "2013",
      "unstructured": "Tourigny, D. S., Fern\u00e1ndez, I. S., Kelley, A. C. & Ramakrishnan, V. Elongation factor G bound to the ribosome in an intermediate state of translocation. Science 340, 1235490 (2013)",
      "journal-title": "Science"
    },
    {
      "key": "BFnature14548_CR45",
      "doi-asserted-by": "crossref",
      "first-page": "219",
      "DOI": "10.1016/j.cell.2014.11.049",
      "volume": "160",
      "author": "Lin. J",
      "year": "2015",
      "unstructured": "Lin. J, Gagnon, M. G., Bulkley, D. & Steitz, T. A. Conformational changes of elongation factor G on the ribosome during tRNA translocation. Cell 160, 219\u2013227 (2015)",
      "journal-title": "Cell"
    },
    {
      "key": "BFnature14548_CR46",
      "doi-asserted-by": "crossref",
      "first-page": "1667",
      "DOI": "10.1093/genetics/155.4.1667",
      "volume": "155",
      "author": "AN Kuhn",
      "year": "2000",
      "unstructured": "Kuhn, A. N. & Brow, D. A. 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\u20131682 (2000)",
      "journal-title": "Genetics"
    },
    {
      "key": "BFnature14548_CR47",
      "first-page": "879",
      "volume": "2",
      "author": "Z Li",
      "year": "1996",
      "unstructured": "Li, Z. & Brow, D. A. A spontaneous duplication in U6 spliceosomal RNA uncouples the early and late functions of the ACAGA element in vivo. RNA 2, 879\u2013894 (1996)",
      "journal-title": "RNA"
    },
    {
      "key": "BFnature14548_CR48",
      "doi-asserted-by": "crossref",
      "first-page": "77",
      "DOI": "10.1126/science.1153803",
      "volume": "320",
      "author": "N Toor",
      "year": "2008",
      "unstructured": "Toor, N., Keating, K. S., Taylor, S. D. & Pyle, A. M. Crystal structure of a self-spliced group II intron. Science 320, 77\u201382 (2008)",
      "journal-title": "Science"
    },
    {
      "key": "BFnature14548_CR49",
      "doi-asserted-by": "crossref",
      "first-page": "464",
      "DOI": "10.1038/nsmb.2815",
      "volume": "21",
      "author": "SM Fica",
      "year": "2013",
      "unstructured": "Fica, S. M., Mefford, M. A., Piccirilli, J. A. & Staley, J. P. Evidence for a group II intron-like catalytic triplex in the spliceosome. Nature Struct. Mol. Biol. 21, 464\u2013471 (2013)",
      "journal-title": "Nature Struct. Mol. Biol."
    },
    {
      "key": "BFnature14548_CR50",
      "doi-asserted-by": "crossref",
      "first-page": "663",
      "DOI": "10.1126/science.1948046",
      "volume": "254",
      "author": "PA Sharp",
      "year": "1991",
      "unstructured": "Sharp, P. A. Five easy pieces. Science 254, 663 (1991)",
      "journal-title": "Science"
    },
    {
      "key": "BFnature14548_CR51",
      "doi-asserted-by": "crossref",
      "first-page": "175",
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