5yzg › Citations

Structure of a human catalytic step I spliceosome.

Zhan X, Yan C, Zhang X, Lei J, Shi Y
Science 359 537-545 (2018)
Cited: 71 times
EuropePMC logo PMID: 29301961

Abstract

Splicing by the spliceosome involves branching and exon ligation. The branching reaction leads to the formation of the catalytic step I spliceosome (C complex). Here we report the cryo-electron microscopy structure of the human C complex at an average resolution of 4.1 angstroms. Compared with the Saccharomyces cerevisiae C complex, the human complex contains 11 additional proteins. The step I splicing factors CCDC49 and CCDC94 (Cwc25 and Yju2 in S. cerevisiae, respectively) closely interact with the DEAH-family adenosine triphosphatase/helicase Prp16 and bridge the gap between Prp16 and the active-site RNA elements. These features, together with structural comparison of the human C and C* complexes, provide mechanistic insights into ribonucleoprotein remodeling and allow the proposition of a working mechanism for the C-to-C* transition.

Reviews - 5yzg mentioned but not cited (2)

  1. Host DDX Helicases as Possible SARS-CoV-2 Proviral Factors: A Structural Overview of Their Hijacking Through Multiple Viral Proteins. Squeglia F, Romano M, Ruggiero A, Maga G, Berisio R. Front Chem 8 602162 (2020)
  2. Structural and Functional Insights into Human Nuclear Cyclophilins. Rajiv C, Davis TL. Biomolecules 8 (2018)

Articles - 5yzg mentioned but not cited (8)

  1. Saccharomyces cerevisiae Ecm2 Modulates the Catalytic Steps of pre-mRNA Splicing. van der Feltz C, Nikolai B, Schneider C, Paulson JC, Fu X, Hoskins AA. RNA rna.077727.120 (2021)
  2. Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes. Busetto V, Barbosa I, Basquin J, Marquenet É, Hocq R, Hennion M, Paternina JA, Namane A, Conti E, Bensaude O, Le Hir H. Nucleic Acids Res. 48 5670-5683 (2020)
  3. The inactive C-terminal cassette of the dual-cassette RNA helicase BRR2 both stimulates and inhibits the activity of the N-terminal helicase unit. Vester K, Santos KF, Kuropka B, Weise C, Wahl MC. J Biol Chem 295 2097-2112 (2020)
  4. A Snu114-GTP-Prp8 module forms a relay station for efficient splicing in yeast. Jia J, Ganichkin OM, Preußner M, Absmeier E, Alings C, Loll B, Heyd F, Wahl MC. Nucleic Acids Res. 48 4572-4584 (2020)
  5. Crystal structure of Prp16 in complex with ADP. Garbers TB, Enders M, Neumann P, Ficner R. Acta Crystallogr F Struct Biol Commun 79 200-207 (2023)
  6. research-article Functional glycoproteomics by integrated network assembly and partitioning. Griffin ME, Thompson JW, Xiao Y, Sweredoski MJ, Aksenfeld RB, Jensen EH, Koldobskaya Y, Schacht AL, Kim TD, Choudhry P, Lomenick B, Garbis SD, Moradian A, Hsieh-Wilson LC. bioRxiv 2023.06.13.541482 (2023)
  7. Structural basis of catalytic activation in human splicing. Schmitzová J, Cretu C, Dienemann C, Urlaub H, Pena V. Nature 617 842-850 (2023)
  8. Structure/epitope analysis and IgE binding activities of three cyclophilin family proteins from Dermatophagoides pteronyssinus. Li Y, Sun X, Yang L. Sci Rep 13 13630 (2023)


Reviews citing this publication (21)

  1. Roles and mechanisms of alternative splicing in cancer - implications for care. Bonnal SC, López-Oreja I, Valcárcel J. Nat Rev Clin Oncol 17 457-474 (2020)
  2. Structural Insights into Nuclear pre-mRNA Splicing in Higher Eukaryotes. Kastner B, Will CL, Stark H, Lührmann R. Cold Spring Harb Perspect Biol 11 a032417 (2019)
  3. Molecular Mechanisms of pre-mRNA Splicing through Structural Biology of the Spliceosome. Yan C, Wan R, Shi Y. Cold Spring Harb Perspect Biol 11 (2019)
  4. DEAH-Box RNA Helicases in Pre-mRNA Splicing. De Bortoli F, Espinosa S, Zhao R. Trends Biochem Sci 46 225-238 (2021)
  5. Eukaryotic Initiation Factor 4A-3: A Review of Its Physiological Role and Involvement in Oncogenesis. Ye J, She X, Liu Z, He Z, Gao X, Lu L, Liang R, Lin Y. Front Oncol 11 712045 (2021)
  6. RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases. Willbanks A, Wood S, Cheng JX. Genes (Basel) 12 627 (2021)
  7. Recent advances and current trends in cryo-electron microscopy. Guaita M, Watters SC, Loerch S. Curr Opin Struct Biol 77 102484 (2022)
  8. Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities. Blijlevens M, Li J, van Beusechem VW. Int J Mol Sci 22 5110 (2021)
  9. Alternative splicing of mRNA in colorectal cancer: new strategies for tumor diagnosis and treatment. Chen Y, Huang M, Liu X, Huang Y, Liu C, Zhu J, Fu G, Lei Z, Chu X. Cell Death Dis 12 752 (2021)
  10. Developments, applications, and prospects of cryo-electron microscopy. Benjin X, Ling L. Protein Sci. 29 872-882 (2020)
  11. Principles and correction of 5'-splice site selection. Malard F, Mackereth CD, Campagne S. RNA Biol 19 943-960 (2022)
  12. Structural advances in transcription elongation. Mohamed AA, Vazquez Nunez R, Vos SM. Curr Opin Struct Biol 75 102422 (2022)
  13. Structural dynamics of the N-terminal domain and the Switch loop of Prp8 during spliceosome assembly and activation. Jia X, Sun C. Nucleic Acids Res. 46 3833-3840 (2018)
  14. Zinc finger structure determination by NMR: Why zinc fingers can be a handful. Neuhaus D. Prog Nucl Magn Reson Spectrosc 130-131 62-105 (2022)
  15. Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus. Kachaev ZM, Ivashchenko SD, Kozlov EN, Lebedeva LA, Shidlovskii YV. Cells 10 3239 (2021)
  16. RBM22, a Key Player of Pre-mRNA Splicing and Gene Expression Regulation, Is Altered in Cancer. Soubise B, Jiang Y, Douet-Guilbert N, Troadec MB. Cancers (Basel) 14 643 (2022)
  17. Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects. Rogalska ME, Vivori C, Valcárcel J. Nat Rev Genet 24 251-269 (2023)
  18. Role of Anillin in Tumour: From a Prognostic Biomarker to a Novel Target. Tuan NM, Lee CH. Cancers (Basel) 12 (2020)
  19. Spliceosome assembly and regulation: insights from analysis of highly reduced spliceosomes. Black CS, Whelan TA, Garside EL, MacMillan AM, Fast NM, Rader SD. RNA 29 531-550 (2023)
  20. The PRP19 Ubiquitin Ligase, Standing at the Cross-Roads of mRNA Processing and Genome Stability. Idrissou M, Maréchal A. Cancers (Basel) 14 878 (2022)
  21. The SF3b Complex is an Integral Component of the Spliceosome and Targeted by Natural Product-Based Inhibitors. Larsen NA. Subcell Biochem 96 409-432 (2021)

Articles citing this publication (40)

  1. Structures of the fully assembled Saccharomyces cerevisiae spliceosome before activation. Bai R, Wan R, Yan C, Lei J, Shi Y. Science 360 1423-1429 (2018)
  2. A human postcatalytic spliceosome structure reveals essential roles of metazoan factors for exon ligation. Fica SM, Oubridge C, Wilkinson ME, Newman AJ, Nagai K. Science 363 710-714 (2019)
  3. Structures of the human pre-catalytic spliceosome and its precursor spliceosome. Zhan X, Yan C, Zhang X, Lei J, Shi Y. Cell Res. 28 1129-1140 (2018)
  4. Structures of the human spliceosomes before and after release of the ligated exon. Zhang X, Zhan X, Yan C, Zhang W, Liu D, Lei J, Shi Y. Cell Res. 29 274-285 (2019)
  5. Cus2 enforces the first ATP-dependent step of splicing by binding to yeast SF3b1 through a UHM-ULM interaction. Talkish J, Igel H, Hunter O, Horner SW, Jeffery NN, Leach JR, Jenkins JL, Kielkopf CL, Ares M. RNA 25 1020-1037 (2019)
  6. Data-guided Multi-Map variables for ensemble refinement of molecular movies. Vant JW, Sarkar D, Streitwieser E, Fiorin G, Skeel R, Vermaas JV, Singharoy A. J Chem Phys 153 214102 (2020)
  7. Atomistic basis of force generation, translocation, and coordination in a viral genome packaging motor. Pajak J, Dill E, Reyes-Aldrete E, White MA, Kelch BA, Jardine PJ, Arya G, Morais MC. Nucleic Acids Res 49 6474-6488 (2021)
  8. Multiple RNA-RNA tertiary interactions are dispensable for formation of a functional U2/U6 RNA catalytic core in the spliceosome. Bao P, Boon KL, Will CL, Hartmuth K, Lührmann R. Nucleic Acids Res. 46 12126-12138 (2018)
  9. Role of the central junction in folding topology of the protein-free human U2-U6 snRNA complex. Chu H, Perea W, Greenbaum NL. RNA 26 836-850 (2020)
  10. Synergistic roles for human U1 snRNA stem-loops in pre-mRNA splicing. Martelly W, Fellows B, Kang P, Vashisht A, Wohlschlegel JA, Sharma S. RNA Biol 18 2576-2593 (2021)
  11. A U2-snRNP-independent role of SF3b in promoting mRNA export. Wang K, Yin C, Du X, Chen S, Wang J, Zhang L, Wang L, Yu Y, Chi B, Shi M, Wang C, Reed R, Zhou Y, Huang J, Cheng H. Proc. Natl. Acad. Sci. U.S.A. 116 7837-7846 (2019)
  12. Global donor and acceptor splicing site kinetics in human cells. Wachutka L, Caizzi L, Gagneur J, Cramer P. Elife 8 (2019)
  13. Sub-2 Angstrom resolution structure determination using single-particle cryo-EM at 200 keV. Wu M, Lander GC, Herzik MA. J Struct Biol X 4 100020 (2020)
  14. A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing. Bergfort A, Preußner M, Kuropka B, Ilik İA, Hilal T, Weber G, Freund C, Aktaş T, Heyd F, Wahl MC. Nat Commun 13 1132 (2022)
  15. BTK, NUTM2A, and PRPF19 Are Novel KMT2A Partner Genes in Childhood Acute Leukemia. Zerkalenkova E, Lebedeva S, Borkovskaia A, Soldatkina O, Plekhanova O, Tsaur G, Maschan M, Maschan A, Novichkova G, Olshanskaya Y. Biomedicines 9 924 (2021)
  16. Identifying RNA splicing factors using IFT genes in Chlamydomonas reinhardtii. Lin H, Zhang Z, Iomini C, Dutcher SK. Open Biol 8 (2018)
  17. Mutations in Spliceosomal Genes PPIL1 and PRP17 Cause Neurodegenerative Pontocerebellar Hypoplasia with Microcephaly. Chai G, Webb A, Li C, Antaki D, Lee S, Breuss MW, Lang N, Stanley V, Anzenberg P, Yang X, Marshall T, Gaffney P, Wierenga KJ, Chung BH, Tsang MH, Pais LS, Lovgren AK, VanNoy GE, Rehm HL, Mirzaa G, Leon E, Diaz J, Neumann A, Kalverda AP, Manfield IW, Parry DA, Logan CV, Johnson CA, Bonthron DT, Valleley EMA, Issa MY, Abdel-Ghafar SF, Abdel-Hamid MS, Jennings P, Zaki MS, Sheridan E, Gleeson JG. Neuron 109 241-256.e9 (2021)
  18. Proteome-wide mapping of short-lived proteins in human cells. Li J, Cai Z, Vaites LP, Shen N, Mitchell DC, Huttlin EL, Paulo JA, Harry BL, Gygi SP. Mol Cell 81 4722-4735.e5 (2021)
  19. Spliceosomal Prp8 intein at the crossroads of protein and RNA splicing. Green CM, Li Z, Smith AD, Novikova O, Bacot-Davis VR, Gao F, Hu S, Banavali NK, Thiele DJ, Li H, Belfort M. PLoS Biol. 17 e3000104 (2019)
  20. A forward genetic screen in C. elegans identifies conserved residues of spliceosomal proteins PRP8 and SNRNP200/BRR2 with a role in maintaining 5' splice site identity. Cartwright-Acar CH, Osterhoudt K, Suzuki JMNGL, Gomez DR, Katzman S, Zahler AM. Nucleic Acids Res 50 11834-11857 (2022)
  21. A molecular brake that modulates spliceosome pausing at detained introns contributes to neurodegeneration. Meng D, Zheng Q, Zhang X, Piao X, Luo L, Jia Y. Protein Cell 14 318-336 (2023)
  22. A two-step probing method to compare lysine accessibility across macromolecular complex conformations. MacRae AJ, Coltri P, Hrabeta-Robinson E, Chalkley RJ, Burlingame AL, Jurica MS. RNA Biol 16 1346-1354 (2019)
  23. Affinity proteomic dissection of the human nuclear cap-binding complex interactome. Dou Y, Kalmykova S, Pashkova M, Oghbaie M, Jiang H, Molloy KR, Chait BT, Rout MP, Fenyö D, Jensen TH, Altukhov I, LaCava J. Nucleic Acids Res 48 10456-10469 (2020)
  24. CRNKL1 Is a Highly Selective Regulator of Intron-Retaining HIV-1 and Cellular mRNAs. Xiao H, Wyler E, Milek M, Grewe B, Kirchner P, Ekici A, Silva ABOV, Jungnickl D, Full F, Thomas M, Landthaler M, Ensser A, Überla K. mBio 12 (2021)
  25. IARA: a complete and curated atlas of the biogenesis of spliceosome machinery during RNA splicing. Rodrigues KS, Petroski LP, Utumi PH, Ferrasa A, Herai RH. Life Sci Alliance 6 e202201593 (2023)
  26. Phytophthora effector PSR1 hijacks the host pre-mRNA splicing machinery to modulate small RNA biogenesis and plant immunity. Gui X, Zhang P, Wang D, Ding Z, Wu X, Shi J, Shen QH, Xu YZ, Ma W, Qiao Y. Plant Cell 34 3443-3459 (2022)
  27. Prp8 impacts cryptic but not alternative splicing frequency. Mayerle M, Yitiz S, Soulette C, Rogel LE, Ramirez A, Ragle JM, Katzman S, Guthrie C, Zahler AM. Proc. Natl. Acad. Sci. U.S.A. 116 2193-2199 (2019)
  28. Regulation of 3' splice site selection after step 1 of splicing by spliceosomal C* proteins. Dybkov O, Preußner M, El Ayoubi L, Feng VY, Harnisch C, Merz K, Leupold P, Yudichev P, Agafonov DE, Will CL, Girard C, Dienemann C, Urlaub H, Kastner B, Heyd F, Lührmann R. Sci Adv 9 eadf1785 (2023)
  29. Structural basis for DEAH-helicase activation by G-patch proteins. Studer MK, Ivanović L, Weber ME, Marti S, Jonas S. Proc. Natl. Acad. Sci. U.S.A. 117 7159-7170 (2020)
  30. Structural insights into branch site proofreading by human spliceosome. Zhang X, Zhan X, Bian T, Yang F, Li P, Lu Y, Xing Z, Fan R, Zhang QC, Shi Y. Nat Struct Mol Biol (2024)
  31. Structure of a SIN3-HDAC complex from budding yeast. Guo Z, Chu C, Lu Y, Zhang X, Xiao Y, Wu M, Gao S, Wong CCL, Zhan X, Wang C. Nat Struct Mol Biol (2023)
  32. Structure of the yeast Swi/Snf complex in a nucleosome free state. Wang C, Guo Z, Zhan X, Yang F, Wu M, Zhang X. Nat Commun 11 3398 (2020)
  33. The SMN complex drives structural changes in human snRNAs to enable snRNP assembly. Pánek J, Roithová A, Radivojević N, Sýkora M, Prusty AB, Huston N, Wan H, Pyle AM, Fischer U, Staněk D. Nat Commun 14 6580 (2023)
  34. The intrinsically disordered TSSC4 protein acts as a helicase inhibitor, placeholder and multi-interaction coordinator during snRNP assembly and recycling. Bergfort A, Hilal T, Kuropka B, Ilik İA, Weber G, Aktaş T, Freund C, Wahl MC. Nucleic Acids Res 50 2938-2958 (2022)
  35. Triple-Negative Breast Cancer circRNAome Reveals Hsa_circ_0072309 as a Potential Risk Biomarker. Magalhães L, Ribeiro-Dos-Santos AM, Cruz RL, Nakamura KDM, Brianese R, Burbano R, Ferreira SP, Oliveira ELF, Anaissi AKM, Nahúm MCS, Demachki S, Vidal AF, Carraro DM, Ribeiro-Dos-Santos Â. Cancers (Basel) 14 3280 (2022)
  36. U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors. Urabe VK, Stevers M, Ghosh AK, Jurica MS. PLoS One 16 e0258551 (2021)
  37. U5 snRNA Interactions With Exons Ensure Splicing Precision. Artemyeva-Isman OV, Porter ACG. Front Genet 12 676971 (2021)
  38. XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence. Hou S, Qu D, Li Y, Zhu B, Liang D, Wei X, Tang W, Zhang Q, Hao J, Guo W, Wang W, Zhao S, Wang Q, Azam S, Khan M, Zhao H, Zhang L, Lei H. Nucleic Acids Res. 47 8239-8254 (2019)
  39. [Frontiers in structural biology]. Yang F, Yang W. Zhejiang Da Xue Xue Bao Yi Xue Ban 48 1-4 (2019)
  40. mRNA Editing, Processing and Quality Control in Caenorhabditis elegans. Arribere JA, Kuroyanagi H, Hundley HA. Genetics 215 531-568 (2020)


Quick links