Structure and function of spliceosomal DEAH-box ATPases.
ATPase
helicase
spliceosome
structure
Journal
Biological chemistry
ISSN: 1437-4315
Titre abrégé: Biol Chem
Pays: Germany
ID NLM: 9700112
Informations de publication
Date de publication:
26 07 2023
26 07 2023
Historique:
received:
10
03
2023
accepted:
04
07
2023
medline:
8
9
2023
pubmed:
13
7
2023
entrez:
13
7
2023
Statut:
epublish
Résumé
Splicing of precursor mRNAs is a hallmark of eukaryotic cells, performed by a huge macromolecular machine, the spliceosome. Four DEAH-box ATPases are essential components of the spliceosome, which play an important role in the spliceosome activation, the splicing reaction, the release of the spliced mRNA and intron lariat, and the disassembly of the spliceosome. An integrative approach comprising X-ray crystallography, single particle cryo electron microscopy, single molecule FRET, and molecular dynamics simulations provided deep insights into the structure, dynamics and function of the spliceosomal DEAH-box ATPases.
Identifiants
pubmed: 37441768
pii: hsz-2023-0157
doi: 10.1515/hsz-2023-0157
doi:
Substances chimiques
Adenosine Triphosphatases
EC 3.6.1.-
Saccharomyces cerevisiae Proteins
0
DEAD-box RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
851-866Informations de copyright
© 2023 the author(s), published by De Gruyter, Berlin/Boston.
Références
Ajmal, M., Khan, M.I., Neveling, K., Khan, Y.M., Azam, M., Waheed, N.K., Hamel, C.P., Ben-Yosef, T., De Baere, E., Koenekoop, R.K., et al.. (2014). A missense mutation in the splicing factor gene DHX38 is associated with early-onset retinitis pigmentosa with macular coloboma. J. Med. Genet. 51: 444–448, https://doi.org/10.1136/jmedgenet-2014-102316 .
doi: 10.1136/jmedgenet-2014-102316
Aravind, L. and Koonin, E.V. (1999). G-patch: a new conserved domain in eukaryotic RNA-processing proteins and type D retroviral polyproteins. Trends Biochem. Sci. 24: 342–344, https://doi.org/10.1016/s0968-0004(99)01437-1 .
doi: 10.1016/s0968-0004(99)01437-1
Arenas, J.E. and Abelson, J.N. (1997). Prp43: an RNA helicase-like factor involved in spliceosome disassembly. Proc. Natl. Acad. Sci. U. S. A. 94: 11798–11802, https://doi.org/10.1073/pnas.94.22.11798 .
doi: 10.1073/pnas.94.22.11798
Bai, R., Wan, R., Yan, C., Jia, Q., Lei, J., and Shi, Y. (2021). Mechanism of spliceosome remodeling by the ATPase/helicase Prp2 and its coactivator Spp2. Science 371: eabe8863, https://doi.org/10.1126/science.abe8863 .
doi: 10.1126/science.abe8863
Bai, R., Yan, C., Wan, R., Lei, J., and Shi, Y. (2017). Structure of the post-catalytic spliceosome from saccharomyces cerevisiae. Cell 171: 1589–1598.
Bao, P., Höbartner, C., Hartmuth, K., and Lührmann, R. (2017). Yeast Prp2 liberates the 5′ splice site and the branch site adenosine for catalysis of pre-mRNA splicing. RNA 23: 1770–1779, https://doi.org/10.1261/rna.063115.117 .
doi: 10.1261/rna.063115.117
Becker, R.A. and Hub, J.S. (2023a). Continuous millisecond conformational cycle of a DEAH box helicase reveals control of domain motions by atomic-scale transitions. Commun. Biol. 6: 379, https://doi.org/10.1038/s42003-023-04751-z .
doi: 10.1038/s42003-023-04751-z
Becker, R.A. and Hub, J.S. (2023b). Molecular simulations of DEAH-box helicases reveal control of domain flexibility by ligands: RNA, ATP, ADP, and G-patch proteins. Biol. Chem. 404: 867–879, https://doi.org/10.1515/hsz-2023-0154 .
doi: 10.1515/hsz-2023-0154
Bertram, K., Agafonov, D.E., Liu, W.T., Dybkov, O., Will, C.L., Hartmuth, K., Urlaub, H., Kastner, B., Stark, H., and Lührmann, R. (2017). Cryo-EM structure of a human spliceosome activated for step 2 of splicing. Nature 542: 318–323.
Bertram, K., El Ayoubi, L., Dybkov, O., Agafonov, D.E., Will, C.L., Hartmuth, K., Urlaub, H., Kastner, B., Stark, H., and Lührmann, R. (2020). Structural insights into the roles of metazoan-specific splicing factors in the human step 1 spliceosome. Mol. Cell 80: 127–139.
Bohnsack, K.E., Ficner, R., Bohnsack, M.T., and Jonas, S. (2021). Regulation of DEAH-box RNA helicases by G-patch proteins. Biol. Chem. 402: 561–579, https://doi.org/10.1515/hsz-2020-0338 .
doi: 10.1515/hsz-2020-0338
Borisek, J., Casalino, L., Saltalamacchia, A., Mays, S.G., Malcovati, L., and Magistrato, A. (2021). Atomic-level mechanism of pre-mRNA Splicing in health and disease. Acc. Chem. Res. 54: 144–154, https://doi.org/10.1021/acs.accounts.0c00578 .
doi: 10.1021/acs.accounts.0c00578
Burgess, S.M. and 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, https://doi.org/10.1016/0092-8674(93)90363-u .
doi: 10.1016/0092-8674(93)90363-u
Chen, J.Y., Stands, L., Staley, J.P., Jackups, R.R.Jr., Latus, L.J., and Chang, T.H. (2001). Specific alterations of U1-C protein or U1 small nuclear RNA can eliminate the requirement of Prp28p, an essential DEAD box splicing factor. Mol. Cell 7: 227–232, https://doi.org/10.1016/s1097-2765(01)00170-8 .
doi: 10.1016/s1097-2765(01)00170-8
Chen, Y.L., Capeyrou, R., Humbert, O., Mouffok, S., Kadri, Y.A., Lebaron, S., Henras, A.K., and Henry, Y. (2014). The telomerase inhibitor Gno1p/PINX1 activates the helicase Prp43p during ribosome biogenesis. Nucleic Acids Res. 42: 7330–7345, https://doi.org/10.1093/nar/gku357 .
doi: 10.1093/nar/gku357
Chen, Z., Gui, B., Zhang, Y., Xie, G., Li, W., Liu, S., Xu, B., Wu, C., He, L., Yang, J, et al.. (2017). Identification of a 35S U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-snRNP) complex intermediate in spliceosome assembly. J. Biol. Chem. 292: 18113–18128, https://doi.org/10.1074/jbc.m117.797357 .
doi: 10.1074/jbc.m117.797357
Christian, H., Hofele, R.V., Urlaub, H., and Ficner, R. (2014). Insights into the activation of the helicase Prp43 by biochemical studies and structural mass spectrometry. Nucleic Acids Res. 42: 1162–1179, https://doi.org/10.1093/nar/gkt985 .
doi: 10.1093/nar/gkt985
Company, M., Arenas, J., and Abelson, J. (1991). Requirement of the RNA helicase-like protein PRP22 for release of messenger RNA from spliceosomes. Nature 349: 487–493, https://doi.org/10.1038/349487a0 .
doi: 10.1038/349487a0
Corsini, L., Bonnal, S., Basquin, J., Hothorn, M., Scheffzek, K., Valcarcel, J., and Sattler, M. (2007). U2AF-homology motif interactions are required for alternative splicing regulation by SPF45. Nat. Struct. Mol. Biol. 14: 620–629, https://doi.org/10.1038/nsmb1260 .
doi: 10.1038/nsmb1260
De Bortoli, F., Espinosa, S., and Zhao, R. (2021). DEAH-Box RNA helicases in pre-mRNA splicing. Trends Biochem. Sci. 46: 225–238, https://doi.org/10.1016/j.tibs.2020.10.006 .
doi: 10.1016/j.tibs.2020.10.006
Enders, M., Ficner, R., and Adio, S. (2022). Regulation of the DEAH/RHA helicase Prp43 by the G-patch factor Pfa1. Proc. Natl. Acad. Sci. U. S. A. 119: e2203567119, https://doi.org/10.1073/pnas.2203567119 .
doi: 10.1073/pnas.2203567119
Enders, M., Ficner, R., and Adio, S. (2023). Conformational dynamics of the RNA binding channel regulates loading and translocation of the DEAH-box helicase Prp43. Nucleic Acids Res. , in press, https://doi.org/10.1093/nar/gkad362 .
doi: 10.1093/nar/gkad362
Felisberto-Rodrigues, C., Thomas, J.C., McAndrew, C., Le Bihan, Y.V., Burke, R., Workman, P., and van Montfort, R.L.M. (2019). Structural and functional characterisation of human RNA helicase DHX8 provides insights into the mechanism of RNA-stimulated ADP release. Biochem. J. 476: 2521–2543, https://doi.org/10.1042/bcj20190383 .
doi: 10.1042/bcj20190383
Fica, S.M., Oubridge, C., Galej, W.P., Wilkinson, M.E., Bai, X.C., Newman, A.J., and Nagai, K. (2017). Structure of a spliceosome remodelled for exon ligation. Nature 542: 377–380, https://doi.org/10.1038/nature21078 .
doi: 10.1038/nature21078
Fica, S.M., Oubridge, C., Wilkinson, M.E., Newman, A.J., and Nagkai, K. (2019). A human postcatalytic spliceosome structure reveals essential roles of metazoan factors for exon ligation. Science 363: 710–714.
Ficner, R., Dickmanns, A., and Neumann, P. (2017). Studying structure and function of spliceosomal helicases. Methods 125: 63–69, https://doi.org/10.1016/j.ymeth.2017.06.028 .
doi: 10.1016/j.ymeth.2017.06.028
Fourmann, J.B., Dybkov, O., Agafonov, D.E., Tauchert, M.J., Urlaub, H., Ficner, R., Fabrizio, P., and Lührmann, R. (2016). The target of the DEAH-box NTP triphosphatase Prp43 in Saccharomyces cerevisiae spliceosomes is the U2 snRNP-intron interaction. eLife 5: e15564, https://doi.org/10.7554/elife.15564 .
doi: 10.7554/elife.15564
Fourmann, J.B., Schmitzova, J., Christian, H., Urlaub, H., Ficner, R., Boon, K.L., Fabrizio, P., and Lührmann, R. (2013). Dissection of the factor requirements for spliceosome disassembly and the elucidation of its dissociation products using a purified splicing system. Genes Dev. 27: 413–428, https://doi.org/10.1101/gad.207779.112 .
doi: 10.1101/gad.207779.112
Fourmann, J.B., Tauchert, M.J., Ficner, R., Fabrizio, P., and Lührmann, R. (2017). Regulation of Prp43-mediated disassembly of spliceosomes by its cofactors Ntr1 and Ntr2. Nucleic Acids Res. 45: 4068–4080, https://doi.org/10.1093/nar/gkw1225 .
doi: 10.1093/nar/gkw1225
Galej, W.P., Wilkinson, M.E., Fica, S.M., Oubridge, C., Newman, A.J., and Nagai, K. (2016). Cryo-EM structure of the spliceosome immediately after branching. Nature 537: 197–201, https://doi.org/10.1038/nature19316 .
doi: 10.1038/nature19316
Garbers, T.B., Enders, M., Neumann, P., and Ficner, R. (2023). Crystal structure of Prp16 in complex with ADP. Acta Crystallogr. F Struct. Biol. Commun. , in press.
Hamann, F., Enders, M., and Ficner, R. (2019). Structural basis for RNA translocation by DEAH-box ATPases. Nucleic Acids Res. 47: 4349–4362, https://doi.org/10.1093/nar/gkz150 .
doi: 10.1093/nar/gkz150
Hamann, F., Schmitt, A., Favretto, F., Hofele, R., Neumann, P., Xiang, S., Urlaub, H., Zweckstetter, M., and Ficner, R. (2020). Structural analysis of the intrinsically disordered splicing factor Spp2 and its binding to the DEAH-box ATPase Prp2. Proc. Natl. Acad. Sci. U. S. A. 117: 2948–2956, https://doi.org/10.1073/pnas.1907960117 .
doi: 10.1073/pnas.1907960117
Hamann, F., Zimmerningkat, L.C., Becker, R.A., Garbers, T.B., Neumann, P., Hub, J.S., and Ficner, R. (2021). The structure of Prp2 bound to RNA and ADP-BeF3− reveals structural features important for RNA unwinding by DEAH-box ATPases. Acta Crystallogr. D Struct. Biol. 77: 496–509, https://doi.org/10.1107/s2059798321001194 .
doi: 10.1107/s2059798321001194
Haselbach, D., Komarov, I., Agafonov, D.E., Hartmuth, K., Graf, B., Dybkov, O., Urlaub, H., Kastner, B., Lührmann, R., and Stark, H. (2018). Structure and conformational dynamics of the human spliceosomal B(act) complex. Cell 172: 454–464.
He, Y., Andersen, G.R., and Nielsen, K.H. (2010). Structural basis for the function of DEAH helicases. EMBO Rep. 11: 180–186, https://doi.org/10.1038/embor.2010.11 .
doi: 10.1038/embor.2010.11
He, Y.Z., Staley, J.P., Andersen, G.R., and Nielsen, K.H. (2017). Structure of the DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of hairpins and motif Va in translocation along RNA. RNA 23: 1110–1124, https://doi.org/10.1261/rna.060954.117 .
doi: 10.1261/rna.060954.117
Hegele, A., Kamburov, A., Grossmann, A., Sourlis, C., Wowro, S., Weimann, M., Will, C.L., Pena, V., Lührmann, R., and Stelzl, U. (2012). Dynamic protein-protein interaction wiring of the human spliceosome. Mol. Cell 45: 567–580, https://doi.org/10.1016/j.molcel.2011.12.034 .
doi: 10.1016/j.molcel.2011.12.034
Heininger, A.U., Hackert, P., Andreou, A.Z., Boon, K.L., Memet, I., Prior, M., Clancy, A., Schmidt, B., Urlaub, H., Schleiff, E, et al.. (2016). Protein cofactor competition regulates the action of a multifunctional RNA helicase in different pathways. RNA Biol. 13: 320–330, https://doi.org/10.1080/15476286.2016.1142038 .
doi: 10.1080/15476286.2016.1142038
Kastner, B., Will, C.L., Stark, H., and Lührmann, R. (2019). Structural Insights into nuclear pre-mRNA splicing in higher eukaryotes. Cold Spring Harb. Perspect. Biol. 11: a032417, https://doi.org/10.1101/cshperspect.a032417 .
doi: 10.1101/cshperspect.a032417
Kim, S.H. and Lin, R.J. (1996). Spliceosome activation by PRP2 ATPase prior to the first transesterification reaction of pre-mRNA splicing. Mol. Cell. Biol. 16: 6810–6819, https://doi.org/10.1128/mcb.16.12.6810 .
doi: 10.1128/mcb.16.12.6810
Kim, S.H., Smith, J., Claude, A., and Lin, R.J. (1992). The purified yeast pre-mRNA splicing factor PRP2 is an RNA-dependent NTPase. EMBO J. 11: 2319–2326, https://doi.org/10.1002/j.1460-2075.1992.tb05291.x .
doi: 10.1002/j.1460-2075.1992.tb05291.x
King, D.S. and Beggs, J.D. (1990). Interactions of PRP2 protein with pre-mRNA splicing complexes in Saccharomyces cerevisiae. Nucleic Acids Res. 18: 6559–6564, https://doi.org/10.1093/nar/18.22.6559 .
doi: 10.1093/nar/18.22.6559
Kistler, A.L. and Guthrie, C. (2001). Deletion of MUD2, the yeast homolog of U2AF65, can bypass the requirement for Sub2, an essential spliceosomal ATPase. Genes Dev. 15: 42–49, https://doi.org/10.1101/gad.851301 .
doi: 10.1101/gad.851301
Kleywegt, G.J. and Jones, T.A. (1996). xdlMAPMAN and xdlDATAMAN – programs for reformatting, analysis and manipulation of biomacromolecular electron-density maps and reflection data sets. Acta Crystallogr. D Biol. Crystallogr. 52: 826–828, https://doi.org/10.1107/s0907444995014983 .
doi: 10.1107/s0907444995014983
Laggerbauer, B., Achsel, T., and Lührmann, R. (1998). The human U5-200kD DEXH-box protein unwinds U4/U6 RNA duplices in vitro. Proc. Natl. Acad. Sci. U. S. A. 95: 4188–4192, https://doi.org/10.1073/pnas.95.8.4188 .
doi: 10.1073/pnas.95.8.4188
Lebaron, S., Papin, C., Capeyrou, R., Chen, Y.L., Froment, C., Monsarrat, B., Caizergues-Ferrer, M., Grigoriev, M., and 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, https://doi.org/10.1038/emboj.2009.335 .
doi: 10.1038/emboj.2009.335
Liu, S., Li, X., Zhang, L., Jiang, J., Hill, R.C., Cui, Y., Hansen, K.C., Zhou, Z.H., and Zhao, R. (2017). Structure of the yeast spliceosomal postcatalytic P complex. Science 358: 1278–1283, https://doi.org/10.1126/science.aar3462 .
doi: 10.1126/science.aar3462
Mayas, R.M., Maita, H., Semlow, D.R., and Staley, J.P. (2010). Spliceosome discards intermediates via the DEAH box ATPase Prp43p. Proc. Natl. Acad. Sci. U. S. A. 107: 10020–10025, https://doi.org/10.1073/pnas.0906022107 .
doi: 10.1073/pnas.0906022107
Movilla, S., Roca, M., Moliner, V., and Magistrato, A. (2023). Molecular basis of RNA-driven ATP hydrolysis in DExH-box helicases. J. Am. Chem. Soc. 145: 6691–6701, https://doi.org/10.1021/jacs.2c11980 .
doi: 10.1021/jacs.2c11980
Murakami, K., Nakano, K., Shimizu, T., and Ohto, U. (2017). The crystal structure of human DEAH-box RNA helicase 15 reveals a domain organization of the mammalian DEAH/RHA family. Acta Crystallogr. F Struct. Biol. Commun. 73: 347–355, https://doi.org/10.1107/s2053230x17007336 .
doi: 10.1107/s2053230x17007336
Niu, Z., Jin, W., Zhang, L., and Li, X. (2012). Tumor suppressor RBM5 directly interacts with the DExD/H-box protein DHX15 and stimulates its helicase activity. FEBS Lett. 586: 977–983, https://doi.org/10.1016/j.febslet.2012.02.052 .
doi: 10.1016/j.febslet.2012.02.052
Obuca, M., Cvackova, Z., Kubovciak, J., Kolar, M., and Stanek, D. (2022). Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity. PLoS One 17: e0265742, https://doi.org/10.1371/journal.pone.0265742 .
doi: 10.1371/journal.pone.0265742
Ozgur, S., Buchwald, G., Falk, S., Chakrabarti, S., Prabu, J.R., and Conti, E. (2015). The conformational plasticity of eukaryotic RNA-dependent ATPases. FEBS J. 282: 850–863, https://doi.org/10.1111/febs.13198 .
doi: 10.1111/febs.13198
Plaschka, C., Newman, A.J., and Nagai, K. (2019). Structural basis of nuclear pre-mRNA splicing: lessons from yeast. Cold Spring Harb. Perspect. Biol. 11: a032391, https://doi.org/10.1101/cshperspect.a032391 .
doi: 10.1101/cshperspect.a032391
Pyle, A.M. (2008). Translocation and unwinding mechanisms of RNA and DNA helicases. Annu. Rev. Biophys. 37: 317–336, https://doi.org/10.1146/annurev.biophys.37.032807.125908 .
doi: 10.1146/annurev.biophys.37.032807.125908
Rauhut, R., Fabrizio, P., Dybkov, O., Hartmuth, K., Pena, V., Chari, A., Kumar, V., Lee, C.T., Urlaub, H., Kastner, B., et al.. (2016). Molecular architecture of the Saccharomyces cerevisiae activated spliceosome. Science 353: 1399–1405.
Robert-Paganin, J., Halladjian, M., Blaud, M., Lebaron, S., Delbos, L., Chardon, F., Capeyrou, R., Humbert, O., Henry, Y., Henras, A.K., et al.. (2017). Functional link between DEAH/RHA helicase Prp43 activation and ATP base binding. Nucleic Acids Res. 45: 1539–1552, https://doi.org/10.1093/nar/gkw1233 .
doi: 10.1093/nar/gkw1233
Roy, J., Kim, K., Maddock, J.R., Anthony, J.G., and Woolford, J.L.Jr. (1995). The final stages of spliceosome maturation require Spp2p that can interact with the DEAH box protein Prp2p and promote step 1 of splicing. RNA 1: 375–390.
Schmitt, A., Hamann, F., Neumann, P., and Ficner, R. (2018). Crystal structure of the spliceosomal DEAH-box ATPase Prp2. Acta Crystallogr. D Struct. Biol. 74: 643–654, https://doi.org/10.1107/s2059798318006356 .
doi: 10.1107/s2059798318006356
Schmitzova, J., Cretu, C., Dienemann, C., Urlaub, H., and Pena, V. (2023). Structural basis of catalytic activation in human splicing. Nature 617: 842–850, https://doi.org/10.1038/s41586-023-06049-w .
doi: 10.1038/s41586-023-06049-w
Schwer, B. (2008). A conformational rearrangement in the spliceosome sets the stage for Prp22-dependent mRNA release. Mol. Cell 30: 743–754, https://doi.org/10.1016/j.molcel.2008.05.003 .
doi: 10.1016/j.molcel.2008.05.003
Semlow, D.R., Blanco, M.R., Walter, N.G., and Staley, J.P. (2016). Spliceosomal DEAH-Box ATPases remodel Pre-mRNA to activate alternative splice sites. Cell 164: 985–998, https://doi.org/10.1016/j.cell.2016.01.025 .
doi: 10.1016/j.cell.2016.01.025
Semlow, D.R. and Staley, J.P. (2012). Staying on message: ensuring fidelity in pre-mRNA splicing. Trends Biochem. Sci. 37: 263–273, https://doi.org/10.1016/j.tibs.2012.04.001 .
doi: 10.1016/j.tibs.2012.04.001
Silverman, E.J., Maeda, A., Wei, J., Smith, P., Beggs, J.D., and Lin, R.J. (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, https://doi.org/10.1128/mcb.24.23.10101-10110.2004 .
doi: 10.1128/mcb.24.23.10101-10110.2004
Sloan, K.E. and Bohnsack, M.T. (2018). Unravelling the mechanisms of RNA helicase regulation. Trends Biochem. Sci. 43: 237–250, https://doi.org/10.1016/j.tibs.2018.02.001 .
doi: 10.1016/j.tibs.2018.02.001
Steimer, L. and Klostermeier, D. (2012). RNA helicases in infection and disease. RNA Biol. 9: 751–771, https://doi.org/10.4161/rna.20090 .
doi: 10.4161/rna.20090
Studer, M.K., Ivanovic, L., Weber, M.E., Marti, S., and Jonas, S. (2020). Structural basis for DEAH-helicase activation by G-patch proteins. Proc. Natl. Acad. Sci. U. S. A. 117: 7159–7170, https://doi.org/10.1073/pnas.1913880117 .
doi: 10.1073/pnas.1913880117
Tanaka, N., Aronova, A., and Schwer, B. (2007). Ntr1 activates the Prp43 helicase to trigger release of lariat-intron from the spliceosome. Genes Dev. 21: 2312–2325, https://doi.org/10.1101/gad.1580507 .
doi: 10.1101/gad.1580507
Tanaka, N. and Schwer, B. (2006). Mutations in PRP43 that uncouple RNA-dependent NTPase activity and pre-mRNA splicing function. Biochemistry 45: 6510–6521, https://doi.org/10.1021/bi052656g .
doi: 10.1021/bi052656g
Tauchert, M.J., Fourmann, J.B., Christian, H., Lührmann, R., and Ficner, R. (2016). Structural and functional analysis of the RNA helicase Prp43 from the thermophilic eukaryote Chaetomium thermophilum. Acta Crystallogr. F Struct. Biol. Commun. 72: 112–120, https://doi.org/10.1107/s2053230x15024498 .
doi: 10.1107/s2053230x15024498
Tauchert, M.J., Fourmann, J.B., Lührmann, R., and Ficner, R. (2017). Structural insights into the mechanism of the DEAH-box RNA helicase Prp43. eLife 6: e21510, https://doi.org/10.7554/elife.21510 .
doi: 10.7554/elife.21510
Tholen, J. and Galej, W.P. (2022). Structural studies of the spliceosome: bridging the gaps. Curr. Opin. Struct. Biol. 77: 102461, https://doi.org/10.1016/j.sbi.2022.102461 .
doi: 10.1016/j.sbi.2022.102461
Tseng, C.K., Liu, H.L., and Cheng, S.C. (2011). DEAH-box ATPase Prp16 has dual roles in remodeling of the spliceosome in catalytic steps. RNA 17: 145–154, https://doi.org/10.1261/rna.2459611 .
doi: 10.1261/rna.2459611
Wagner, J.D., Jankowsky, E., Company, M., Pyle, A.M., and Abelson, J.N. (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, https://doi.org/10.1093/emboj/17.10.2926 .
doi: 10.1093/emboj/17.10.2926
Wahl, M.C., Will, C.L., and Lührmann, R. (2009). The spliceosome: design principles of a dynamic RNP machine. Cell 136: 701–718, https://doi.org/10.1016/j.cell.2009.02.009 .
doi: 10.1016/j.cell.2009.02.009
Walbott, H., Mouffok, S., Capeyrou, R., Lebaron, S., Humbert, O., van Tilbeurgh, H., Henry, Y., and Leulliot, N. (2010). Prp43p contains a processive helicase structural architecture with a specific regulatory domain. EMBO J. 29: 2194–2204, https://doi.org/10.1038/emboj.2010.102 .
doi: 10.1038/emboj.2010.102
Wan, R., Bai, R., and Shi, Y. (2019). Molecular choreography of pre-mRNA splicing by the spliceosome. Curr. Opin. Struct. Biol. 59: 124–133, https://doi.org/10.1016/j.sbi.2019.07.010 .
doi: 10.1016/j.sbi.2019.07.010
Wan, R., Yan, C., Bai, R., Lei, J., and Shi, Y. (2017). Structure of an intron lariat spliceosome from Saccharomyces cerevisiae. Cell 171: 120–132.e112, https://doi.org/10.1016/j.cell.2017.08.029 .
doi: 10.1016/j.cell.2017.08.029
Wang, Y., Wagner, J.D., and Guthrie, C. (1998). The DEAH-box splicing factor Prp16 unwinds RNA duplexes in vitro. Curr. Biol. 8: 441–451, https://doi.org/10.1016/s0960-9822(98)70178-2 .
doi: 10.1016/s0960-9822(98)70178-2
Warkocki, Z., Schneider, C., Mozaffari-Jovin, S., Schmitzova, J., Hobartner, C., Fabrizio, P., and Lührmann, R. (2015). 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, https://doi.org/10.1101/gad.253070.114 .
doi: 10.1101/gad.253070.114
Wilkinson, M.E., Charenton, C., and Nagai, K. (2020). RNA splicing by the spliceosome. Annu. Rev. Biochem. 89: 359–388, https://doi.org/10.1146/annurev-biochem-091719-064225 .
doi: 10.1146/annurev-biochem-091719-064225
Wilkinson, M.E., Fica, S.M., Galej, W.P., and Nagai, K. (2021). Structural basis for conformational equilibrium of the catalytic spliceosome. Mol. Cell 81: 1439–1452.e1439, https://doi.org/10.1016/j.molcel.2021.02.021 .
doi: 10.1016/j.molcel.2021.02.021
Wilkinson, M.E., Fica, S.M., Galej, W.P., Norman, C.M., Newman, A.J., and Nagkai, K. (2017). Postcatalytic spliceosome structure reveals mechanism of 3’-splice site selection. Science 358: 1283–1288.
Will, C.L. and Lührmann, R. (2011). Spliceosome structure and function. Cold Spring Harb. Perspect. Biol. 3: 181–203, https://doi.org/10.1101/cshperspect.a003707 .
doi: 10.1101/cshperspect.a003707
Xu, Y.Z. and Query, C.C. (2007). Competition between the ATPase Prp5 and branch region-U2 snRNA pairing modulates the fidelity of spliceosome assembly. Mol. Cell 28: 838–849, https://doi.org/10.1016/j.molcel.2007.09.022 .
doi: 10.1016/j.molcel.2007.09.022
Yan, C., Wan, R., Bai, R., Huang, G., and Shi, Y. (2016). Structure of a yeast activated spliceosome at 3.5 A resolution. Science 353: 904–911.
Yan, C., Wan, R., Bai, R., Huang, G., and Shi, Y. (2017). Structure of a yeast step II catalytically activated spliceosome. Science 355: 149–155.
Yan, C., Wan, R., and Shi, Y. (2019). Molecular mechanisms of pre-mRNA splicing through structural biology of the spliceosome. Cold Spring Harb. Perspect. Biol. 11: a032409, https://doi.org/10.1101/cshperspect.a032409 .
doi: 10.1101/cshperspect.a032409
Yoshimoto, R., Kataoka, N., Okawa, K., and Ohno, M. (2009). Isolation and characterization of post-splicing lariat-intron complexes. Nucleic Acids Res. 37: 891–902, https://doi.org/10.1093/nar/gkn1002 .
doi: 10.1093/nar/gkn1002
Zang, S., Lin, T.Y., Chen, X., Gencheva, M., Newo, A.N., Yang, L., Rossi, D., Hu, J., Lin, S.B., Huang, A., et al.. (2014). GPKOW is essential for pre-mRNA splicing in vitro and suppresses splicing defect caused by dominant-negative DHX16 mutation in vivo. Biosci. Rep. 34: e00163, https://doi.org/10.1042/bsr20140142 .
doi: 10.1042/bsr20140142
Zhan, X., Lu, Y., Zhang, X., Yan, C., and Shi, Y. (2022). Mechanism of exon ligation by human spliceosome. Mol. Cell 82: 2769–2778.
Zhan, X., Yan, C., Zhang, X., Lei, J., and Shi, Y. (2018). Structure of a human catalytic step I spliceosome. Science 359: 537–545, https://doi.org/10.1126/science.aar6401 .
doi: 10.1126/science.aar6401
Zhang, J., Huang, J., Xu, K., Xing, P., Huang, Y., Liu, Z., Tong, L., and Manley, J.L. (2022). DHX15 is involved in SUGP1-mediated RNA missplicing by mutant SF3B1 in cancer. Proc. Natl. Acad. Sci. U. S. A. 119: e2216712119, https://doi.org/10.1073/pnas.2216712119 .
doi: 10.1073/pnas.2216712119
Zhang, X., Yan, C., Hang, J., Finci, L.I., Lei, J., and Shi, Y (2017). An atomic structure of the human spliceosome. Cell 169: 918–929.
Zhang, X., Yan, C., Zhan, X., Lei, J., and Shi, Y. (2018). Structure of the human activated spliceosome in three conformational states. Cell Res. 28: 307–322.
Zhang, X., Zhan, X., Yan, C., Zhang, W., Liu, D., Lei, J., and Shi, Y. (2019). Structures of the human spliceosomes before and after release of the ligated exon. Cell Res. 29: 274–285.