Structure and conformational dynamics of the human spliceosomal Bact complex
Open accessAbstract
The spliceosome is a highly dynamic macromolecular complex that precisely excises introns from pre-mRNA. Here we report the cryo-EM 3D structure of the human B act spliceosome at 3.4 Å resolution. In the B act state, the spliceosome is activated but not catalytically primed, so that it is functionally blocked prior to the first catalytic step of splicing. The spliceosomal core is similar to the yeast B act spliceosome; important differences include the presence of the RNA helicase aquarius and peptidyl prolyl isomerases. To examine the overall dynamic behavior of the purified spliceosome, we developed a principal component analysis-based approach. Calculating the energy landscape revealed eight major conformational states, which we refined to higher resolution. Conformational differences of the highly flexible structural components between these eight states reveal how spliceosomal components contribute to the assembly of the spliceosome, allowing it to generate a dynamic interaction network required for its subsequent catalytic activation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The CCCH-type zinc finger of RNF113A associates with the 5′ splice site of pre-mRNAs in the active spliceosome.
“the CCCH-type zinc-finger associates with the 5´ splice site of pre-mRNAs in the active spliceosome”
From Aberrant RNA methylation triggers recruitment of an alkylation repair complex (2021) · cites this paper as Haselbach et al., 2018
The RNF113A section (p. 7) places its N-terminal zinc finger in direct contact with the pre-mRNA 5′ splice site. The Introduction (p. 2), however, identifies the studied Bact complex as activated but pre-catalytic, not a catalytically active spliceosome. Our copy calls the domain a zinc finger but does not identify it as CCCH-type. (LLM, conf=0.85)
Experimental — accuracy not yet measuredStructural studies have shown that RNF113A and its yeast orthologue Cwc24p associate with the spliceosome.
“Structural studies on RNF113A and its yeast orthologue Cwc24p have demonstrated spliceosomal association”
From Aberrant RNA methylation triggers recruitment of an alkylation repair complex (2021) · cites this paper as Haselbach et al., 2018
The section “RNF113A Connects Several Spatially Separated Parts” (p. 7) places RNF113A within the human Bact spliceosome and describes its contacts with other spliceosomal proteins. The passages do not identify Cwc24p as its yeast orthologue or establish Cwc24p’s spliceosomal association, so the citation supports only the RNF113A part of the claim. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,260 · see citing works
<i>Coot</i> : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
<i>PHENIX</i> : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716 · see citing works
SWISS‐MODEL and the Swiss‐Pdb Viewer: An environment for comparative protein modeling
Guex, N., & Peitsch, M. (1997) · Electrophoresis · doi:10.1002/elps.1150181505 · Cited by 11,589 · see citing works
Dignam, J. D., Lebovitz, R. M., & Roeder, R. G. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.5.1475 · Cited by 11,262 · see citing works
MotionCor2 - anisotropic correction of beam-induced motion for improved cryo-electron microscopy
Zheng, S., Palovcak, E. J., Armache, J., Verba, K., Cheng, Y.-F., & Agard, D. (2017) · Nature Methods · doi:10.1038/nmeth.4193 · Cited by 7,678 · see citing works
RELION: Implementation of a Bayesian approach to cryo-EM structure determination
Scheres, S. H. W. (2012) · Journal of Structural Biology · doi:10.1016/j.jsb.2012.09.006 · Cited by 5,446 · see citing works
Gctf: Real-time CTF determination and correction
Zhang, K. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.11.003 · Cited by 3,372 · see citing works
EMAN2: An extensible image processing suite for electron microscopy
Tang, G., Peng, L., Baldwin, P. R., Mann, D. S., Jiang, W., Rees, I., & Ludtke, S. J. (2006) · Journal of Structural Biology · doi:10.1016/j.jsb.2006.05.009 · Cited by 2,914 · see citing works
The Spliceosome: Design Principles of a Dynamic RNP Machine
Wahl, M. C., Will, C. L., & Lührmann, R. (2009) · Cell · doi:10.1016/j.cell.2009.02.009 · Cited by 2,665 · see citing works
Self-citationScalable web services for the PSIPRED Protein Analysis Workbench
Buchan, D. W. A., Minneci, F., Nugent, T. C. O., Bryson, K., & Jones, D. T. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt381 · Cited by 1,321 · see citing works
Jurica, M. S., & Moore, M. J. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00270-3 · Cited by 963 · see citing works
Visualizing density maps with UCSF Chimera
Goddard, T. D., Huang, C. C., & Ferrin, T. E. (2006) · Journal of Structural Biology · doi:10.1016/j.jsb.2006.06.010 · Cited by 876 · see citing works
GraFix: sample preparation for single-particle electron cryomicroscopy
Kastner, B., Fischer, N., Golas, M. M., Sander, B. O., Dube, P., Boehringer, D., Hartmuth, K., Deckert, J., Hauer, F., Wolf, E., et al. (2007) · Nature Methods · doi:10.1038/nmeth1139 · Cited by 578 · see citing works
Self-citationIdentification of cross-linked peptides from complex samples
Yang, B., Wu, Y.-J., Zhu, M., Fan, S., Lin, J., Zhang, K., Li, S., Chi, H., Li, Y., Chen, H., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2099 · Cited by 574 · see citing works
Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy
Fischer, N., Konevega, A. L., Wintermeyer, W., Rodnina, M. V., & Stark, H. (2010) · Nature · doi:10.1038/nature09206 · Cited by 434 · see citing works
Self-citationSmall Nuclear Ribonucleoprotein Remodeling During Catalytic Activation of the Spliceosome
Makarov, E. M., Makarova, O. V., Urlaub, H., Gentzel, M., Will, C. L., Wilm, M. S., & Lührmann, R. (2002) · Science · doi:10.1126/science.1077783 · Cited by 374 · see citing works
Self-citationRNA catalyses nuclear pre-mRNA splicing
Fica, S. M., Tuttle, N., Novak, T., Li, N., Lu, J., Koodathingal, P., Dai, Q., Staley, J. P., & Piccirilli, J. A. (2013) · Nature · doi:10.1038/nature12734 · Cited by 348 · see citing works
The Prp19p-Associated Complex in Spliceosome Activation
Chan, S., Kao, D.-I., Tsai, W.-Y., & Cheng, S.-C. (2003) · Science · doi:10.1126/science.1086602 · Cited by 323 · see citing works
The Evolutionarily Conserved Core Design of the Catalytic Activation Step of the Yeast Spliceosome
Fabrizio, P., Dannenberg, J., Dube, P., Kastner, B., Stark, H., Urlaub, H., & Lührmann, R. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.040 · Cited by 313 · see citing works
Self-citationLeitner, A., Walzthoeni, T., & Aebersold, R. H. (2013) · Nature Protocols · doi:10.1038/nprot.2013.168 · Cited by 275 · see citing works
An Atomic Structure of the Human Spliceosome
Zhang, X., Yan, C., Hang, J., Finci, L. I., Lei, J., & Shi, Y. (2017) · Cell · doi:10.1016/j.cell.2017.04.033 · Cited by 268 · see citing works
Structure of a yeast activated spliceosome at 3.5 Å resolution
Yan, C., Wan, R., Bai, R., Huang, G., & Shi, Y. (2016) · Science · doi:10.1126/science.aag0291 · Cited by 261 · see citing works
Cryo-EM Structure of a Pre-catalytic Human Spliceosome Primed for Activation
Bertram, K., Agafonov, D. E., Dybkov, O., Haselbach, D., Leelaram, M. N., Will, C. L., Urlaub, H., Kastner, B., Lührmann, R., & Stark, H. (2017) · Cell · doi:10.1016/j.cell.2017.07.011 · Cited by 261 · see citing works
Self-citationMetal-ion coordination by U6 small nuclear RNA contributes to catalysis in the spliceosome
Yean, S.-L., Wuenschell, G. E., Termini, J. S., & Lin, R.-J. (2000) · Nature · doi:10.1038/35048617 · Cited by 254 · see citing works
Cryo-EM structure of a human spliceosome activated for step 2 of splicing
Bertram, K., Agafonov, D. E., Liu, W.-T., Dybkov, O., Will, C. L., Hartmuth, K., Urlaub, H., Kastner, B., Stark, H., & Lührmann, R. (2017) · Nature · doi:10.1038/nature21079 · Cited by 251 · see citing works
Self-citationMolecular Architecture of SF3b and Structural Consequences of Its Cancer-Related Mutations
Cretu, C., Schmitzová, J., Ponce-Salvatierra, A., Dybkov, O., Laurentiis, E. I. D., Sharma, K., Will, C. L., Urlaub, H., Lührmann, R., & Peña, V. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.08.036 · Cited by 242 · see citing works
Self-citationThe architecture of the spliceosomal U4/U6.U5 tri-snRNP
Nguyen, T. H. D., Galej, W. P., Bai, X., Savva, C. G., Newman, A. J., Scheres, S. H. W., & Nagai, K. (2015) · Nature · doi:10.1038/nature14548 · Cited by 240 · see citing works
Agafonov, D. E., Deckert, J., Wolf, E., et al. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05266-11 · Cited by 238 · see citing works
Self-citationCryo-EM structure of the spliceosome immediately after branching
Galej, W. P., Wilkinson, M. E., Fica, S. M., Oubridge, C., Newman, A. J., & Nagai, K. (2016) · Nature · doi:10.1038/nature19316 · Cited by 235 · see citing works
Structure of a pre-catalytic spliceosome
Plaschka, C., Lin, P.-C., & Nagai, K. (2017) · Nature · doi:10.1038/nature22799 · Cited by 217 · see citing works
Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution
Nguyen, T. H. D., Galej, W. P., Bai, X., Oubridge, C., Newman, A. J., Scheres, S. H. W., & Nagai, K. (2016) · Nature · doi:10.1038/nature16940 · Cited by 215 · see citing works
Structural basis of pre-mRNA splicing
Hang, J., Wan, R., Yan, C., & Shi, Y. (2015) · Science · doi:10.1126/science.aac8159 · Cited by 195 · see citing works
Molecular architecture of the human U4/U6.U5 tri-snRNP
Agafonov, D. E., Kastner, B., Dybkov, O., Hofele, R. V., Liu, W.-T., Urlaub, H., Lührmann, R., & Stark, H. (2016) · Science · doi:10.1126/science.aad2085 · Cited by 195 · see citing works
Self-citationStructure of a yeast catalytic step I spliceosome at 3.4 Å resolution
Wan, R., Yan, C., Bai, R., Huang, G., & Shi, Y. (2016) · Science · doi:10.1126/science.aag2235 · Cited by 173 · see citing works
Molecular architecture of the Saccharomyces cerevisiae activated spliceosome
Rauhut, R., Fabrizio, P., Dybkov, O., Hartmuth, K., Peña, V., Chari, A., Kumar, V., Lee, C., Urlaub, H., Kastner, B., et al. (2016) · Science · doi:10.1126/science.aag1906 · Cited by 169 · see citing works
Self-citationStructure of a spliceosome remodelled for exon ligation
Fica, S. M., Oubridge, C., Galej, W. P., Wilkinson, M. E., Bai, X., Newman, A. J., & Nagai, K. (2017) · Nature · doi:10.1038/nature21078 · Cited by 169 · see citing works
Bessonov, S., Anokhina, M. M., Krasauskas, A., Golas, M. M., Sander, B. O., Will, C. L., Urlaub, H., Stark, H., & Lührmann, R. (2010) · RNA · doi:10.1261/rna.2456210 · Cited by 159 · see citing works
Self-citationKim, S.-H., & Lin, R.-J. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.12.6810 · Cited by 155 · see citing works
Structure of a yeast step II catalytically activated spliceosome
Yan, C., Wan, R., Bai, R., Huang, G., & Shi, Y. (2016) · Science · doi:10.1126/science.aak9979 · Cited by 138 · see citing works
Postcatalytic spliceosome structure reveals mechanism of 3′–splice site selection
Wilkinson, M. E., Fica, S. M., Galej, W. P., Norman, C. M., Newman, A. J., & Nagai, K. (2017) · Science · doi:10.1126/science.aar3729 · Cited by 119 · see citing works
Evidence for a group II intron–like catalytic triplex in the spliceosome
Fica, S. M., Mefford, M. A., Piccirilli, J. A., & Staley, J. P. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2815 · Cited by 103 · see citing works
Structure of the yeast spliceosomal postcatalytic P complex
Liu, S., Li, X., Zhang, L., Jiang, J., Hill, R. C., Cui, Y., Hansen, K. C., Zhou, Z. H., & Zhao, R. (2017) · Science · doi:10.1126/science.aar3462 · Cited by 103 · see citing works
Structure of an Intron Lariat Spliceosome from Saccharomyces cerevisiae
Wan, R., Yan, C., Bai, R., Lei, J., & Shi, Y. (2017) · Cell · doi:10.1016/j.cell.2017.08.029 · Cited by 98 · see citing works
Structure of the Post-catalytic Spliceosome from Saccharomyces cerevisiae
Bai, R., Yan, C., Wan, R., Lei, J., & Shi, Y. (2017) · Cell · doi:10.1016/j.cell.2017.10.038 · Cited by 95 · see citing works
Intrinsic Disorder in the Human Spliceosomal Proteome
Korneta, I., & Bujnicki, J. M. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002641 · Cited by 93 · see citing works
The RNA helicase Aquarius exhibits structural adaptations mediating its recruitment to spliceosomes
De, I., Bessonov, S., Hofele, R., dos Santos, K., Will, C. L., Urlaub, H., Lührmann, R., & Pena, V. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2951 · Cited by 89 · see citing works
Self-citationHaselbach, D., Schrader, J., Lambrecht, F., Henneberg, F., Chari, A., & Stark, H. (2017) · Nature Communications · doi:10.1038/ncomms15578 · Cited by 79 · see citing works
Self-citationCrystal structure of a core spliceosomal protein interface
Schellenberg, M. J., Edwards, R. A., Ritchie, D. B., Kent, O. A., Golas, M. M., Stark, H., Lührmann, R., Glover, J. N. M., & MacMillan, A. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508048103 · Cited by 75 · see citing works
Self-citationL30 Binds the Nascent RPL30 Transcript to Repress U2 snRNP Recruitment
Macías, S., Bragulat, M., Tardiff, D. F., & Vilardell, J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.05.002 · Cited by 60 · see citing works
Structure and assembly of the SF3a splicing factor complex of U2 snRNP
Lin, P.-C., & Xu, R.-M. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.7 · Cited by 51 · see citing works
Xu, C., Zhang, J., Huang, X., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511155200 · Cited by 40 · see citing works
Kuwasako, K., He, F., Inoue, M., et al. (2006) · Structure · doi:10.1016/j.str.2006.09.009 · Cited by 29 · see citing works
Structure and evolution of the spliceosomal peptidyl-prolylcis–transisomerase Cwc27
Ulrich, A. K. C., & Wahl, M. C. (2014) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s1399004714021695 · Cited by 22 · see citing works
Crystal structure of U2 snRNP SF3b components: Hsh49p in complex with Cus1p-binding domain
van Roon, A. M., Oubridge, C., OBAYASHI, E., Sposito, B., Newman, A. J., Séraphin, B., & Nagai, K. (2017) · RNA · doi:10.1261/rna.059378.116 · Cited by 16 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Chan, S.-P., Kao, D.-I., Tsai, W.-Y., and Cheng, S.-C. (2003). The Prp19pAssociated Complex in Spliceosome Activation. Science 302 , 279-282. http://refhub.elsevier.com/S0092-8674(1830047-3/sref9)
- van Roon, A.-M.A.M., Oubridge, C., Obayashi, E., Sposito, B., Newman, A.J., Seraphin, B., and Nagai, K. (2017). Crystal structure of U2 snRNP SF3b components:Hsh49pincomplexwithCus1pbindingdomain.RNA 23 , 968-981. http://refhub.elsevier.com/S0092-8674(1830047-3/sref41)
Cited by
Sorted by citations
Aberrant RNA methylation triggers recruitment of an alkylation repair complex
Tsao, N., Brickner, J. R., Rodell, R., Ganguly, A., Wood, M., Oyeniran, C., Ahmad, T., Sun, H., Bacolla, A., Zhang, L., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.09.024 · Cited by 46 · see citing works
Townley, B. A., Buerer, L., Tsao, N., Bacolla, A., Mansoori, F., Rusanov, T., Clark, N. E., Goodarzi, N., Schmidt, N., Srivatsan, S. N., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.06.011 · Cited by 15 · see citing works
- Authors
- Haselbach, D., Komarov, I., Agafonov, D. E., Hartmuth, K., Graf, B., Dybkov, O., Urlaub, H., Kastner, B., Lührmann, R., & Stark, H.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Lührmann, Reinhard
- Stark, Holger
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 172
- Issue
- 3
- Pages
- 454-464.e11
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2784237640
- Semantic Scholar
- 11c627925bf33a1f58e793f62c45de6310fcb895
- Cited by
- 218
- References
- 55
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 17 · 2023: 23 · 2022: 37 · 2021: 31 · 2020: 33 · 2019: 38 · 2018: 14
- FWCI
- 10.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- spliceosome, cryo-EM structure, conformational dynamics, spliceosome assembly, peptidyl-prolyl isomerase, principal component analysis, energy landscape, intron excision, pre-mRNA splicing, catalytic activation
- MeSH terms
- HeLa Cells, Humans, Spliceosomes, Molecular Dynamics Simulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
