Structure of activated transcription complex Pol II–DSIF–PAF–SPT6
Open accessAbstract
Gene regulation involves activation of RNA polymerase II (Pol II) that is paused and bound by the protein complexes DRB sensitivity-inducing factor (DSIF) and negative elongation factor (NELF). Here we show that formation of an activated Pol II elongation complex in vitro requires the kinase function of the positive transcription elongation factor b (P-TEFb) and the elongation factors PAF1 complex (PAF) and SPT6. The cryo-EM structure of an activated elongation complex of Sus scrofa Pol II and Homo sapiens DSIF, PAF and SPT6 was determined at 3.1 Å resolution and compared to the structure of the paused elongation complex formed by Pol II, DSIF and NELF. PAF displaces NELF from the Pol II funnel for pause release. P-TEFb phosphorylates the Pol II linker to the C-terminal domain. SPT6 binds to the phosphorylated C-terminal-domain linker and opens the RNA clamp formed by DSIF. These results provide the molecular basis for Pol II pause release and elongation activation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Spt6 binds to the phosphorylated RNA Pol II CTD and facilitates RNA Pol II promoter-proximal pause release.
“Spt6 binds to the phosphorylated RNA Pol II CTD and facilitates RNA Pol II promoter‐proximal pause release (Vos et al, 2018a).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Vos et al, 2018a
Cites
MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability
Katoh, K., & Standley, D. M. (2013) · Molecular Biology and Evolution · doi:10.1093/molbev/mst010 · Cited by 46,209 · see citing works
<i>Phaser</i> crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612 · see citing works
The Phyre2 web portal for protein modeling, prediction and analysis
Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N., & Sternberg, M. J. E. (2015) · Nature Protocols · doi:10.1038/nprot.2015.053 · Cited by 9,652 · see citing works
Wada, T., Takagi, T., Yamaguchi, Y., Ferdous, A., Imai, T., Hirose, S., Sugimoto, S., Yano, K., Hartzog, G. A., Winston, F., et al. (1998) · Genes & Development · doi:10.1101/gad.12.3.343 · Cited by 750 · see citing works
Control of RNA Polymerase II Elongation Potential by a Novel Carboxyl-terminal Domain Kinase
Marshall, N. F., Peng, J., Xie, Z., & Price, D. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.43.27176 · Cited by 662 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Gene regulation by long non-coding RNAs and its biological functions
Statello, L., Guo, C.-J., Chen, L.-L., & Huarte, M. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00315-9 · Cited by 4,991 · see citing works
Krajewska, M., Dries, R., Grassetti, A. V., Dust, S., Gao, Y., Huang, H., Sharma, B., Day, D. S., Kwiatkowski, N., Pomaville, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09703-y · Cited by 281 · see citing works
Cortazar, M. A., Sheridan, R. M., Erickson, B., Fong, N., Glover-Cutter, K., Brannan, K., & Bentley, D. L. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.031 · Cited by 227 · see citing works
RNA polymerase II speed: a key player in controlling and adapting transcriptome composition
Muniz, L., Nicolas, E., & Trouche, D. (2021) · The EMBO Journal · doi:10.15252/embj.2020105740 · Cited by 203 · see citing works
“Spt6 binds to the phosphorylated RNA Pol II CTD and facilitates RNA Pol II promoter-proximal pause release (Vos et al , 2018a).”
Huang, K.-L., Jee, D., Stein, C. B., Elrod, N. D., Henriques, T., Mascibroda, L. G., Baillat, D., Russell, W. K., Adelman, K., & Wagner, E. J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.08.016 · Cited by 184 · see citing works
Structure of complete Pol II–DSIF–PAF–SPT6 transcription complex reveals RTF1 allosteric activation
Vos, S. M., Farnung, L., Linden, A., Urlaub, H., & Cramer, P. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0437-1 · Cited by 160 · see citing works
Self-citationPaf1C regulates RNA polymerase II progression by modulating elongation rate
Hou, L., Wang, Y., Liu, Y., Zhang, N., Shamovsky, I., Nudler, E., Tian, B., & Dynlacht, B. D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1904324116 · Cited by 129 · see citing works
A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes
Maslon, M. M., Braunschweig, U., Aitken, S., Mann, A. R., Kilanowski, F., Hunter, C. J., Blencowe, B. J., Kornblihtt, A. R., Adams, I. R., & Cáceres, J. F. (2019) · The EMBO Journal · doi:10.15252/embj.2018101244 · Cited by 63 · see citing works
A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair
van den Heuvel, D., Spruijt, C. G., González-Prieto, R., Kragten, A., Paulsen, M. T., Zhou, D., Wu, H., Apelt, K., van der Weegen, Y., Yang, K., et al. (2020) · doi:10.1101/2020.01.04.894808 · Cited by 69 · see citing works
In vitro analysis of RNA polymerase II elongation complex dynamics
Joo, Y. J., Ficarro, S. B., Chun, Y., Marto, J. A., & Buratowski, S. (2019) · Genes & Development · doi:10.1101/gad.324202.119 · Cited by 44 · see citing works
Genetic interaction mapping informs integrative structure determination of protein complexes
Braberg, H., Echeverria, I., Bohn, S., Cimermancic, P., Shiver, A., Alexander, R., Xu, J., Shales, M., Dronamraju, R., Jiang, S., et al. (2020) · Science · doi:10.1126/science.aaz4910 · Cited by 37 · see citing works
Defining the roles of the Integrator, NEXT, and nuclear exosome complexes in Drosophila oogenesis
Lee, Y., Biasini, A., Tipping, C., Hong, S. H., & Zamore, P. D. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116329 · Cited by 6 · see citing works
- Authors
- Vos, S. M., Farnung, L., Boehning, M., Wigge, C., Linden, A., Urlaub, H., & Cramer, P.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Cramer, Patrick
- Venue
- Nature
- Published
- 2018-08-22
- Volume
- 560
- Issue
- 7720
- Pages
- 607-612
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2888537731
- Cited by
- 432
- References
- 5
- Citations by year
- 2026: 49 · 2025: 47 · 2024: 77 · 2023: 41 · 2022: 57 · 2021: 58 · 2020: 41 · 2019: 54 · 2018: 8
- FWCI
- 14.15
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- RNA polymerase II, transcription elongation, DSIF, NELF, P-TEFb, Paf1 complex, Spt6, C-terminal domain phosphorylation, transcriptional pause, cryo-EM structure, Sus scrofa, human
- MeSH terms
- Animals, DNA, Humans, Models, Molecular, Nuclear Proteins, Phosphoproteins, RNA, RNA Polymerase II, Transcription Factors, Cryoelectron Microscopy, Sus scrofa, Transcriptional Elongation Factors, Positive Transcriptional Elongation Factor B, Transcription Elongation, Genetic
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
