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Everything at once: cryo-EM yields remarkable insights into human RNA polymerase II transcription

Nature Structural & Molecular Biology volume 28, pages 540–543 (2021)Cite this article

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After years of only low-resolution and partial assemblies, the entire human preinitiation complex (PIC), including the large and flexible Mediator and TFIID complexes, has come into focus. Five recent papers from three different research groups have transformed our understanding of transcription initiation by RNA polymerase II.

Since the discovery of RNA polymerase II (Pol II)1, structural data lagged behind the biochemical and cellular studies that established fundamental aspects of Pol II function and its regulation by associated factors. Among the myriad Pol II–associated factors, a core set is required to direct it to transcription start sites on genomic DNA and to control Pol II activity once it is bound to these sites. This core set of factors is known as the preinitiation complex (PIC), comprising TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, Pol II and Mediator2. The PIC is approximately 4 MDa in size and its Mediator, TFIID and TFIIH components are both large and structurally dynamic. This presents many challenges for structural biologists, but these challenges have been overcome by the He3, Cramer4,5 and Xu6,7 groups, who report high-resolution structures of the complete human PIC for the first time.

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Fig. 1: Comparison of recent PIC and Mediator–PIC structures.
Fig. 2: Model of the Pol II CTD path to Mediator and CDK7.
Fig. 3: Selected structural details important for Pol II transcription initiation.

References

  1. Roeder, R. G. Nat. Struct. Mol. Biol. 26, 783–791 (2019).

    Article  CAS  Google Scholar 

  2. Schier, A. C. & Taatjes, D. J. Genes Dev. 34, 465–488 (2020).

    Article  CAS  Google Scholar 

  3. Abdella, R. et al. Science 372, 52–56 (2021).

    Article  CAS  Google Scholar 

  4. Aibara, S., Schilbach, S. & Cramer, P. Nature https://doi.org/10.1038/s41586-021-03554-8 (2021).

  5. Rengachari, S., Schilbach, S., Aibara, S., Dienemann, C. & Cramer, P. Nature https://doi.org/10.1038/s41586-021-03555-7 (2021).

  6. Chen, X. et al. Science 372, eaba8490 (2021).

    Article  CAS  Google Scholar 

  7. Chen, X. et al. Science https://doi.org/10.1126/science.abg0635 (2021).

  8. Robinson, P. J. et al. Cell 166, 1411–1422.e16 (2016).

    Article  CAS  Google Scholar 

  9. Schilbach, S. et al. Nature 551, 204–209 (2017).

    Article  CAS  Google Scholar 

  10. Tsai, K.-L. et al. Nature 544, 196–201 (2017).

    Article  CAS  Google Scholar 

  11. Zhao, H. et al. Nat. Commun. 12, 1355 (2021).

    Article  CAS  Google Scholar 

  12. Søgaard, T. M. M. & Svejstrup, J. Q. J. Biol. Chem. 282, 14113–14120 (2007).

    Article  Google Scholar 

  13. Patel, A. B. et al. Science 362, eaau8872 (2018).

    Article  CAS  Google Scholar 

  14. Fishburn, J., Tomko, E., Galburt, E. & Hahn, S. Proc. Natl Acad. Sci. USA 112, 3961–3966 (2015).

    Article  CAS  Google Scholar 

  15. Tomko, E. J. et al. J. Mol. Biol. https://doi.org/10.1016/j.jmb.2021.166813 (2021).

  16. Rossi, M. J. et al. Nature 592, 309–314 (2021).

    Article  CAS  Google Scholar 

  17. Taatjes, D. J., Näär, A. M., Andel, F. III, Nogales, E. & Tjian, R. Science 295, 1058–1062 (2002).

    Article  CAS  Google Scholar 

  18. Henley, M. J. et al. Proc. Natl Acad. Sci. USA 117, 27346–27353 (2020).

    Article  CAS  Google Scholar 

  19. Rodriguez, J. & Larson, D. R. Annu. Rev. Biochem. 89, 189–212 (2020).

    Article  CAS  Google Scholar 

  20. Gressel, S. et al. Elife 6, e29736 (2017).

    Article  Google Scholar 

  21. Shao, W. & Zeitlinger, J. Nat. Genet. 49, 1045–1051 (2017).

    Article  CAS  Google Scholar 

  22. Tantale, K. et al. Nat. Commun. 7, 12248 (2016).

    Article  CAS  Google Scholar 

  23. Sabari, B. R., Dall’Agnese, A. & Young, R. A. Trends Biochem. Sci. 45, 961–977 (2020).

    Article  CAS  Google Scholar 

  24. Takahashi, H. et al. Cell 146, 92–104 (2011).

    Article  CAS  Google Scholar 

  25. Greber, B. J., Toso, D. B., Fang, J. & Nogales, E. Elife 8, e44771 (2019).

    Article  Google Scholar 

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  1. Dept. of Biochemistry, University of Colorado, Boulder, CO, USA

    Allison C. Schier & Dylan J. Taatjes

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  1. Allison C. Schier
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Correspondence to Dylan J. Taatjes.

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D.J.T. is a member of the scientific advisory board at Dewpoint Therapeutics.

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Schier, A.C., Taatjes, D.J. Everything at once: cryo-EM yields remarkable insights into human RNA polymerase II transcription. Nat Struct Mol Biol 28, 540–543 (2021). https://doi.org/10.1038/s41594-021-00613-6

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