Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The pol II CTD: new twists in the tail

Abstract

The C-terminal domain (CTD) of the large subunit of RNA polymerase (pol) II comprises conserved heptad repeats, and post-translational modification of the CTD regulates transcription and cotranscriptional RNA processing. Recently, the spatial patterns of modification of the CTD repeats have been investigated, and new functions of CTD modification have been revealed. In addition, there are new insights into the roles of the enzymes that decorate the CTD. We review these new findings and reassess the role of the pol II CTD in the regulation of gene expression.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Modifications of consensus and nonconsensus CTD repeats and their functions.
Figure 2: Patterns of CTD modification across protein-coding genes.
Figure 3
Figure 4: CDK9 is a master regulator driving transcription forward.

Similar content being viewed by others

References

  1. Eick, D. & Geyer, M. The RNA polymerase II carboxy-terminal domain (CTD) code. Chem. Rev. 113, 8456–8490 (2013).

    CAS  PubMed  Google Scholar 

  2. Jeronimo, C., Collin, P. & Robert, F. The RNA polymerase II CTD: the increasing complexity of a low-complexity protein domain. J. Mol. Biol. 428, 2607–2622 (2016).

    CAS  PubMed  Google Scholar 

  3. Srivastava, R. & Ahn, S.H. Modifications of RNA polymerase II CTD: connections to the histone code and cellular function. Biotechnol. Adv. 33, 856–872 (2015).

    CAS  PubMed  Google Scholar 

  4. Egloff, S., Dienstbier, M. & Murphy, S. Updating the RNA polymerase CTD code: adding gene-specific layers. Trends Genet. 28, 333–341 (2012).

    Article  CAS  PubMed  Google Scholar 

  5. Voss, K. et al. Site-specific methylation and acetylation of lysine residues in the C-terminal domain (CTD) of RNA polymerase II. Transcription 6, 91–101 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Dias, J.D. et al. Methylation of RNA polymerase II non-consensus lysine residues marks early transcription in mammalian cells. eLife 4, e11215 (2015).

    PubMed  PubMed Central  Google Scholar 

  7. Li, H. et al. Wwp2-mediated ubiquitination of the RNA polymerase II large subunit in mouse embryonic pluripotent stem cells. Mol. Cell. Biol. 27, 5296–5305 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Sims, R.J. III. et al. The C-terminal domain of RNA polymerase II is modified by site-specific methylation. Science 332, 99–103 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhao, D.Y. et al. SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination. Nature 529, 48–53 (2016).

    PubMed  Google Scholar 

  10. Hintermair, C. et al. Threonine-4 of mammalian RNA polymerase II CTD is targeted by Polo-like kinase 3 and required for transcriptional elongation. EMBO J. 31, 2784–2797 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Descostes, N. et al. Tyrosine phosphorylation of RNA polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells. eLife 3, e02105 (2014).

    PubMed  PubMed Central  Google Scholar 

  12. Nojima, T. et al. Mammalian NET-seq reveals genome-wide nascent transcription coupled to RNA processing. Cell 161, 526–540 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Milligan, L. et al. Strand-specific, high-resolution mapping of modified RNA polymerase II. Mol. Syst. Biol. 12, 874 (2016).

    PubMed  PubMed Central  Google Scholar 

  14. Churchman, L.S. & Weissman, J.S. Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature 469, 368–373 (2011).

    CAS  PubMed  Google Scholar 

  15. Lu, L. et al. Distributive O-GlcNAcylation on the highly repetitive C-terminal domain of RNA polymerase II. Biochemistry 55, 1149–1158 (2016).

    CAS  PubMed  Google Scholar 

  16. Mayer, A. et al. CTD tyrosine phosphorylation impairs termination factor recruitment to RNA polymerase II. Science 336, 1723–1725 (2012).

    CAS  PubMed  Google Scholar 

  17. Harlen, K.M. et al. Comprehensive RNA polymerase II interactomes reveal distinct and varied roles for each phospho-CTD residue. Cell Rep. 15, 2147–2158 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Bataille, A.R. et al. A universal RNA polymerase II CTD cycle is orchestrated by complex interplays between kinase, phosphatase, and isomerase enzymes along genes. Mol. Cell 45, 158–170 (2012).

    CAS  PubMed  Google Scholar 

  19. Mayer, A. et al. Uniform transitions of the general RNA polymerase II transcription complex. Nat. Struct. Mol. Biol. 17, 1272–1278 (2010).

    CAS  PubMed  Google Scholar 

  20. Tietjen, J.R. et al. Chemical-genomic dissection of the CTD code. Nat. Struct. Mol. Biol. 17, 1154–1161 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Kim, H. et al. Gene-specific RNA polymerase II phosphorylation and the CTD code. Nat. Struct. Mol. Biol. 17, 1279–1286 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Suh, H. et al. Direct analysis of phosphorylation sites on the Rpb1 C-terminal domain of RNA polymerase II. Mol. Cell 61, 297–304 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Schüller, R. et al. Heptad-specific phosphorylation of RNA P=polymerase II CTD. Mol. Cell 61, 305–314 (2016).

    PubMed  Google Scholar 

  24. Stiller, J.W. & Cook, M.S. Functional unit of the RNA polymerase II C-terminal domain lies within heptapeptide pairs. Eukaryot. Cell 3, 735–740 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Akhtar, M.S. et al. TFIIH kinase places bivalent marks on the carboxy-terminal domain of RNA polymerase II. Mol. Cell 34, 387–393 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Glover-Cutter, K. et al. TFIIH-associated Cdk7 kinase functions in phosphorylation of C-terminal domain Ser7 residues, promoter-proximal pausing, and termination by RNA polymerase II. Mol. Cell. Biol. 29, 5455–5464 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Galbraith, M.D., Donner, A.J. & Espinosa, J.M. CDK8: a positive regulator of transcription. Transcription 1, 4–12 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Galbraith, M.D. et al. HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia. Cell 153, 1327–1339 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Poss, Z.C. et al. Identification of Mediator kinase substrates in human cells using cortistatin a and quantitative phosphoproteomics. Cell Rep. 15, 436–450 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Bartkowiak, B. et al. CDK12 is a transcription elongation-associated CTD kinase, the metazoan ortholog of yeast Ctk1. Genes Dev. 24, 2303–2316 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pei, Y., Schwer, B. & Shuman, S. Interactions between fission yeast Cdk9, its cyclin partner Pch1, and mRNA capping enzyme Pct1 suggest an elongation checkpoint for mRNA quality control. J. Biol. Chem. 278, 7180–7188 (2003).

    CAS  PubMed  Google Scholar 

  32. Karagiannis, J. & Balasubramanian, M.K. A cyclin-dependent kinase that promotes cytokinesis through modulating phosphorylation of the carboxy terminal domain of the RNA Pol II Rpb1p sub-unit. PLoS One 2, e433 (2007).

    PubMed  PubMed Central  Google Scholar 

  33. Laitem, C. et al. CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II–transcribed genes. Nat. Struct. Mol. Biol. 22, 396–403 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Greifenberg, A.K. et al. Structural and functional analysis of the Cdk13/Cyclin K complex. Cell Rep. 14, 320–331 (2016).

    CAS  PubMed  Google Scholar 

  35. Ghamari, A. et al. In vivo live imaging of RNA polymerase II transcription factories in primary cells. Genes Dev. 27, 767–777 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Czudnochowski, N., Bösken, C.A. & Geyer, M. Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition. Nat. Commun. 3, 842 (2012).

    PubMed  Google Scholar 

  37. Blazek, D. et al. The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev. 25, 2158–2172 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Bowman, E.A., Bowman, C.R., Ahn, J.H. & Kelly, W.G. Phosphorylation of RNA polymerase II is independent of P-TEFb in the C. elegans germline. Development 140, 3703–3713 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Cheng, S.W. et al. Interaction of cyclin-dependent kinase 12/CrkRS with cyclin K1 is required for the phosphorylation of the C-terminal domain of RNA polymerase II. Mol. Cell. Biol. 32, 4691–4704 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Davidson, L., Muniz, L. & West, S. 3′ end formation of pre-mRNA and phosphorylation of Ser2 on the RNA polymerase II CTD are reciprocally coupled in human cells. Genes Dev. 28, 342–356 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Eifler, T.T. et al. Cyclin-dependent kinase 12 increases 3′ end processing of growth factor-induced c-FOS transcripts. Mol. Cell. Biol. 35, 468–478 (2015).

    PubMed  Google Scholar 

  42. Yu, M. et al. RNA polymerase II-associated factor 1 regulates the release and phosphorylation of paused RNA polymerase II. Science 350, 1383–1386 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Liang, K. et al. Characterization of human cyclin-dependent kinase 12 (CDK12) and CDK13 complexes in C-terminal domain phosphorylation, gene transcription, and RNA processing. Mol. Cell. Biol. 35, 928–938 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Bartkowiak, B., Yan, C. & Greenleaf, A.L. Engineering an analog-sensitive CDK12 cell line using CRISPR/Cas. Biochim. Biophys. Acta 1849, 1179–1187 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Bösken, C.A. et al. The structure and substrate specificity of human Cdk12/Cyclin K. Nat. Commun. 5, 3505 (2014).

    PubMed  Google Scholar 

  46. Di Vona, C. et al. Chromatin-wide profiling of DYRK1A reveals a role as a gene-specific RNA polymerase II CTD kinase. Mol. Cell 57, 506–520 (2015).

    CAS  PubMed  Google Scholar 

  47. Pak, V. et al. CDK11 in TREX/THOC regulates HIV mRNA 3′ end processing. Cell Host Microbe 18, 560–570 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Devaiah, B.N. et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc. Natl. Acad. Sci. USA 109, 6927–6932 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Hsin, J.P., Sheth, A. & Manley, J.L. RNAP II CTD phosphorylated on threonine-4 is required for histone mRNA 3′ end processing. Science 334, 683–686 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Baskaran, R., Escobar, S.R. & Wang, J.Y. Nuclear c-Abl is a COOH-terminal repeated domain (CTD)-tyrosine (CTD)-tyrosine kinase-specific for the mammalian RNA polymerase II: possible role in transcription elongation. Cell Growth Differ. 10, 387–396 (1999).

    CAS  PubMed  Google Scholar 

  51. Schröder, S. et al. Acetylation of RNA polymerase II regulates growth-factor-induced gene transcription in mammalian cells. Mol. Cell 52, 314–324 (2013).

    PubMed  PubMed Central  Google Scholar 

  52. Mosley, A.L. et al. Rtr1 is a CTD phosphatase that regulates RNA polymerase II during the transition from serine 5 to serine 2 phosphorylation. Mol. Cell 34, 168–178 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Egloff, S., Zaborowska, J., Laitem, C., Kiss, T. & Murphy, S. Ser7 phosphorylation of the CTD recruits the RPAP2 Ser5 phosphatase to snRNA genes. Mol. Cell 45, 111–122 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Ni, Z. et al. RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation. Nat. Struct. Mol. Biol. 21, 686–695 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Krishnamurthy, S., He, X., Reyes-Reyes, M., Moore, C. & Hampsey, M. Ssu72 Is an RNA polymerase II CTD phosphatase. Mol. Cell 14, 387–394 (2004).

    CAS  PubMed  Google Scholar 

  56. Zhang, D.W. et al. Ssu72 phosphatase-dependent erasure of phospho-Ser7 marks on the RNA polymerase II C-terminal domain is essential for viability and transcription termination. J. Biol. Chem. 287, 8541–8551 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. O'Reilly, D. et al. Human snRNA genes use polyadenylation factors to promote efficient transcription termination. Nucleic Acids Res. 42, 264–275 (2014).

    CAS  PubMed  Google Scholar 

  58. Cho, E.J., Kobor, M.S., Kim, M., Greenblatt, J. & Buratowski, S. Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain. Genes Dev. 15, 3319–3329 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Schreieck, A. et al. RNA polymerase II termination involves C-terminal-domain tyrosine dephosphorylation by CPF subunit Glc7. Nat. Struct. Mol. Biol. 21, 175–179 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Hsu, P.L. et al. Rtr1 is a dual specificity phosphatase that dephosphorylates Tyr1 and Ser5 on the RNA polymerase II CTD. J. Mol. Biol. 426, 2970–2981 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. McCracken, S. et al. The C-terminal domain of RNA polymerase II couples mRNA processing to transcription. Nature 385, 357–361 (1997).

    CAS  PubMed  Google Scholar 

  62. Grzechnik, P., Gdula, M.R. & Proudfoot, N.J. Pcf11 orchestrates transcription termination pathways in yeast. Genes Dev. 29, 849–861 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Burugula, B.B. et al. Histone deacetylases and phosphorylated polymerase II C-terminal domain recruit Spt6 for cotranscriptional histone reassembly. Mol. Cell. Biol. 34, 4115–4129 (2014).

    PubMed  PubMed Central  Google Scholar 

  64. Hintermair, C. et al. Specific threonine-4 phosphorylation and function of RNA polymerase II CTD during M phase progression. Sci. Rep. 6, 27401 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Simonti, C.N. et al. Evolution of lysine acetylation in the RNA polymerase II C-terminal domain. BMC Evol. Biol. 15, 35 (2015).

    PubMed  PubMed Central  Google Scholar 

  66. Ranuncolo, S.M., Ghosh, S., Hanover, J.A., Hart, G.W. & Lewis, B.A. Evidence of the involvement of O-GlcNAc-modified human RNA polymerase II CTD in transcription in vitro and in vivo. J. Biol. Chem. 287, 23549–23561 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Brès, V., Yoh, S.M. & Jones, K.A. The multi-tasking P-TEFb complex. Curr. Opin. Cell Biol. 20, 334–340 (2008).

    PubMed  PubMed Central  Google Scholar 

  68. Zaborowska, J., Isa, N.F. & Murphy, S. P-TEFb goes viral. Inside Cell 1, 106–116 (2016).

    PubMed  Google Scholar 

  69. Kwak, H. & Lis, J.T. Control of transcriptional elongation. Annu. Rev. Genet. 47, 483–508 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. O'Brien, S.K., Cao, H., Nathans, R., Ali, A. & Rana, T.M. P-TEFb kinase complex phosphorylates histone H1 to regulate expression of cellular and HIV-1 genes. J. Biol. Chem. 285, 29713–29720 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Kim, J.B. & Sharp, P.A. Positive transcription elongation factor B phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase. J. Biol. Chem. 276, 12317–12323 (2001).

    CAS  PubMed  Google Scholar 

  72. Shchebet, A., Karpiuk, O., Kremmer, E., Eick, D. & Johnsen, S.A. Phosphorylation by cyclin-dependent kinase-9 controls ubiquitin-conjugating enzyme-2A function. Cell Cycle 11, 2122–2127 (2012).

    CAS  PubMed  Google Scholar 

  73. Sansó, M. et al. P-TEFb regulation of transcription termination factor Xrn2 revealed by a chemical genetic screen for Cdk9 substrates. Genes Dev. 30, 117–131 (2016).

    PubMed  PubMed Central  Google Scholar 

  74. Chen, F.X. et al. PAF1, a molecular regulator of promoter-proximal pausing by RNA polymerase II. Cell 162, 1003–1015 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Chathoth, K.T., Barrass, J.D., Webb, S. & Beggs, J.D. A splicing-dependent transcriptional checkpoint associated with prespliceosome formation. Mol. Cell 53, 779–790 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Fong, Y.W. & Zhou, Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature 414, 929–933 (2001).

    CAS  PubMed  Google Scholar 

  77. Koga, M., Hayashi, M. & Kaida, D. Splicing inhibition decreases phosphorylation level of Ser2 in Pol II CTD. Nucleic Acids Res. 43, 8258–8267 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Yoh, S.M., Cho, H., Pickle, L., Evans, R.M. & Jones, K.A. The Spt6 SH2 domain binds Ser2-P RNAPII to direct Iws1-dependent mRNA splicing and export. Genes Dev. 21, 160–174 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Vasiljeva, L., Kim, M., Mutschler, H., Buratowski, S. & Meinhart, A. The Nrd1–Nab3–Sen1 termination complex interacts with the Ser5-phosphorylated RNA polymerase II C-terminal domain. Nat. Struct. Mol. Biol. 15, 795–804 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Noble, C.G. et al. Key features of the interaction between Pcf11 CID and RNA polymerase II CTD. Nat. Struct. Mol. Biol. 12, 144–151 (2005).

    CAS  PubMed  Google Scholar 

  81. Werner-Allen, J.W. et al. cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72. J. Biol. Chem. 286, 5717–5726 (2011).

    CAS  PubMed  Google Scholar 

  82. Kubicek, K. et al. Serine phosphorylation and proline isomerization in RNAP II CTD control recruitment of Nrd1. Genes Dev. 26, 1891–1896 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Rosonina, E. et al. Threonine-4 of the budding yeast RNAP II CTD couples transcription with Htz1-mediated chromatin remodeling. Proc. Natl. Acad. Sci. USA 111, 11924–11931 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Lewis, B.A. O-GlcNAcylation at promoters, nutrient sensors, and transcriptional regulation. Biochim. Biophys. Acta 1829, 1202–1206 (2013).

    CAS  PubMed  Google Scholar 

  85. Chatterjee, D., Sanchez, A.M., Goldgur, Y., Shuman, S. & Schwer, B. Transcription of lncRNA prt, clustered prt RNA sites for Mmi1 binding, and RNA polymerase II CTD phospho-sites govern the repression of pho1 gene expression under phosphate-replete conditions in fission yeast. RNA 22, 1011–1025 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Coudreuse, D. et al. A gene-specific requirement of RNA polymerase II CTD phosphorylation for sexual differentiation in S. pombe. Curr. Biol. 20, 1053–1064 (2010).

    CAS  PubMed  Google Scholar 

  87. Clemente-Blanco, A. et al. Cdc14 phosphatase promotes segregation of telomeres through repression of RNA polymerase II transcription. Nat. Cell Biol. 13, 1450–1456 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Kim, M., Suh, H., Cho, E.J. & Buratowski, S. Phosphorylation of the yeast Rpb1 C-terminal domain at serines 2, 5, and 7. J. Biol. Chem. 284, 26421–26426 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Zhang, M. et al. Structural and kinetic analysis of prolyl-isomerization/phosphorylation cross-talk in the CTD code. ACS Chem. Biol. 7, 1462–1470 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Wani, S., Sugita, A., Ohkuma, Y. & Hirose, Y. Human SCP4 is a chromatin-associated CTD phosphatase and exhibits the dynamic translocation during erythroid differentiation. J. Biochem. 160, 111–120 (2016).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank L. Vasiljeva, N. Proudfoot, M. Tellier and I. Ferrer-Vicens for discussions and critical comments. The authors also thank F. Vazquez-Arango and M. Tellier for assistance with generating figures. This work was supported by grants from the Wellcome Trust (WT106134A) to S.M. and by Fondation ARC to S.E.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shona Murphy.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zaborowska, J., Egloff, S. & Murphy, S. The pol II CTD: new twists in the tail. Nat Struct Mol Biol 23, 771–777 (2016). https://doi.org/10.1038/nsmb.3285

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb.3285

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing