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PreprintCited by 12Genomics and Chromatin DynamicsDNA Repair MechanismsRNA Research and Splicing

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Structural basis of RECQL5-induced RNA polymerase II transcription braking and subsequent reactivation

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Zhang, Luojia, Gordiyenko, Yuliya, Morgan, Tomos, Franco, Catarina, Vidaković, Ana Tufegdžić, Zhang, Suyang·2025·Nature Structural & Molecular Biology
DOI 10.1101/2025.01.29.635449PMC PMC12440807

Preprint — published as 10.1038/s41594-025-01586-6 · Paper page

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Abstract

During productive transcription elongation, the speed of RNA polymerase II (Pol II) is highly dynamic within individual genes and varies between different genes 1,2 . Unregulated rapid transcription elongation can lead to detrimental consequences such as transcription-replication collisions, altered alternative splicing patterns, and genome instability 1–7 . Therefore, elongating Pol II requires mechanisms to slow its progression, yet the molecular basis of transcription braking remains unclear. RECQL5 is a DNA helicase that functions as a general elongation factor by slowing down Pol II 8–11 . Here we report cryo-electron microscopy (cryo-EM) structures of human RECQL5 bound to multiple transcription elongation complexes. Combined with biochemical analysis, we identify an α-helix of RECQL5 responsible for Pol II binding and slowdown of transcription elongation. We further reveal that the transcription-coupled DNA repair (TCR) complex allows Pol II to overcome RECQL5-induced transcription braking through concerted actions of its translocase activity and competition with RECQL5 for engaging Pol II. Additionally, RECQL5 inhibits TCR-mediated Pol II ubiquitination to prevent activation of the DNA repair pathway. Our results suggest a model in which RECQL5 and the TCR complex coordinately regulate the transcription elongation rate to ensure transcription efficiency while maintaining genome stability. This work provides a framework for future studies on the regulatory role of elongation speed in gene expression.

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  1. 10.15252/embj.2020105740 · DOI · Paper page
  2. 10.1038/nrm3953 · DOI · Paper page
  3. 10.1016/j.molcel.2021.01.040 · DOI
  4. 10.1101/gr.225615.117 · DOI · Paper page
  5. Kotsantis, P. et al. Increased global transcription activity as a mechanism of replication stress in cancer. Nat Commun 7, 13087 (2016). · DOI
  6. 10.1016/j.molcel.2003.08.001 · DOI · Paper page
  7. 10.1016/j.molcel.2014.03.044 · DOI
  8. 10.1074/jbc.M109.015750 · DOI
  9. 10.1038/nsmb.2596 · DOI
  10. 10.1016/j.cell.2014.03.048 · DOI · Paper page
  11. 10.1042/BJ20071392 · DOI
  12. 10.1016/j.molcel.2006.06.014 · DOI · Paper page
  13. 10.1038/s41586-018-0440-4 · DOI · Paper page
  14. 10.1128/MCB.26.10.3986-3996.2006 · DOI
  15. 10.1016/j.molcel.2012.10.014 · DOI
  16. 10.1016/j.molcel.2010.11.005 · DOI · Paper page
  17. 10.1016/j.celrep.2013.08.013 · DOI · Paper page
  18. 10.7554/eLife.02407 · DOI · Paper page
  19. 10.1146/annurev-genet-102209-163602 · DOI
  20. 10.1073/pnas.0804424105 · DOI
  21. 10.1101/gad.1609107 · DOI
  22. 10.1128/MCB.25.9.3431-3442.2005 · DOI
  23. Andrs, M. , Hasanova, Z. , Oravetzova, A. , Dobrovolna, J. & Janscak, P . RECQ5: A Mysterious Helicase at the Interface of DNA Replication and Transcription. Genes (Basel) 11(2020). · DOI
  24. 10.1074/jbc.M110.110478 · DOI
  25. 10.1093/nar/gkp147 · DOI
  26. 10.1093/nar/gkl677 · DOI
  27. Hamadeh, Z. & Lansdorp, P . RECQL5 at the Intersection of Replication and Transcription. Front Cell Dev Biol 8, 324 (2020). · DOI
  28. Lu, H. & Davis, A.J . Human RecQ Helicases in DNA Double-Strand Break Repair. Front Cell Dev Biol 9, 640755 (2021). · DOI
  29. 10.1128/MCB.25.8.3305-3316.2005 · DOI
  30. 10.1093/nar/gkq697 · DOI
  31. 10.1016/j.febslet.2014.10.014 · DOI
  32. Islam, M.N. , Fox, D ., 3rd, Guo, R. , Enomoto, T. & Wang, W. RecQL5 promotes genome stabilization through two parallel mechanisms--interacting with RNA polymerase II and acting as a helicase. Mol Cell Biol 30, 2460-72 (2010). · DOI
  33. 10.1101/gad.200303.112 · DOI
  34. Heidemann, M. , Hintermair, C. , Voss, K. & Eick, D . Dynamic phosphorylation patterns of RNA polymerase II CTD during transcription. Biochim Biophys Acta 1829, 55–62 (2013). · DOI
  35. 10.1126/science.abf1870 · DOI
  36. 10.1016/j.molcel.2022.06.027 · DOI
  37. 10.1038/nature09785 · DOI · Paper page
  38. 10.1038/s41594-023-01207-0 · DOI
  39. 10.1038/s41556-021-00688-9 · DOI · Paper page
  40. 10.1038/nature24658 · DOI
  41. 10.1073/pnas.94.21.11205 · DOI
  42. 10.1371/journal.pgen.1004284 · DOI
  43. 10.1038/s41586-021-03906-4 · DOI
  44. 10.1073/pnas.072068399 · DOI
  45. van der Weegen, Y. et al. The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II. Nat Commun 11, 2104 (2020). · DOI
  46. 10.1016/j.cell.2020.02.010 · DOI
  47. 10.1016/j.cell.2020.02.009 · DOI
  48. 10.1101/gad.378206 · DOI · Paper page
  49. Maslon, M.M. et al. A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes. EMBO J 38(2019). · DOI · Paper page
  50. 10.1073/pnas.1408964111 · DOI · Paper page
  51. 10.1016/j.celrep.2017.11.006 · DOI · Paper page
  52. 10.1038/emboj.2013.167 · DOI · Paper page
  53. Li, M. et al. SUMO2 conjugation of PCNA facilitates chromatin remodeling to resolve transcription-replication conflicts. Nat Commun 9, 2706 (2018). · DOI
  54. 10.1128/MCB.01137-10 · DOI
  55. 10.1073/pnas.94.9.4306 · DOI
  56. 10.1128/MCB.17.12.6803 · DOI
  57. 10.1093/emboj/16.19.5955 · DOI
  58. 10.1016/bs.mie.2017.03.008 · DOI
  59. Liu, H. & Naismith, J.H . An efficient one-step site-directed deletion, insertion, single and multiple-site plasmid mutagenesis protocol. BMC Biotechnol 8, 91 (2008). · DOI
  60. 10.1016/j.jmb.2011.11.010 · DOI
  61. 10.1016/bs.mie.2016.04.012 · DOI
  62. 10.1038/s41592-019-0580-y · DOI
  63. 10.1038/nmeth.4169 · DOI · Paper page
  64. 10.1002/jcc.20084 · DOI
  65. 10.1107/S0907444910007493 · DOI · Paper page
  66. 10.1107/S2059798319011471/HTTPS://GOLDBOOK.IUPAC.ORG/E02002.HTML · DOI
  67. 10.1038/s41586-024-07215-4 · DOI · Paper page
  68. 10.1093/nar/gkad180 · DOI
  69. 10.1002/pro.3235 · DOI · Paper page
  70. Waterhouse, A.M. , Procter, J.B. , Martin, D.M. , Clamp, M. & Barton, G.J. Jalview Version 2--a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189-91 (2009). · DOI
  71. 10.1038/S41596-018-0082-X · DOI
  72. 10.1074/mcp.TIR118.001270 · DOI
  73. 10.1038/nbt.2377 · DOI
  74. 10.15252/msb.20198994 · DOI
  75. Combe, C.W. , Graham, M. , Kolbowski, L. , Fischer, L. & Rappsilber, J . xiVIEW: Visualisation of Crosslinking Mass Spectrometry Data. J Mol Biol 436, 168656 (2024). · DOI
  76. 10.1002/PRO.3902 · DOI

Metadata

Authors
Zhang, L., Gordiyenko, Y., Morgan, T., Franco, C., Vidaković, A. T., & Zhang, S.
Affiliations
MRC Laboratory of Molecular Biology (GB)
Corresponding author
Zhang, Suyang
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
openRxiv
Published
2025-01-31
Volume
32
Issue
9
Pages
1731-1740
ISSN
1545-9985 (ISSN-L)
DOI
10.1101/2025.01.29.635449
PMC
PMC12440807
OpenAlex
W4412093902
Cited by
12
References
1
Citations by year
2026: 8 · 2025: 4
FWCI
3.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Structural & Molecular Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Apollo (University of Cambridge) (acceptedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
RECQL5, RNA polymerase II, transcription elongation, transcription elongation complex, DNA helicase, transcription-coupled repair, genome stability, alternative splicing, cryo-EM structure
MeSH terms
DNA Repair, Humans, Models, Molecular, Protein Binding, RNA Polymerase II, Transcription, Genetic, Cryoelectron Microscopy, RecQ Helicases, Ubiquitination, Transcription Elongation, Genetic

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