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Structure and mechanism of the RNA polymerase II transcription machinery

Abstract

Advances in structure determination of the bacterial and eukaryotic transcription machinery have led to a marked increase in the understanding of the mechanism of transcription. Models for the specific assembly of the RNA polymerase II transcription machinery at a promoter, conformational changes that occur during initiation of transcription, and the mechanism of initiation are discussed in light of recent developments.

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Figure 1: The pathway of transcription initiation and reinitiation for RNA Pol II.
Figure 2: General transcription factor structures.
Figure 3: The ten-subunit yeast RNA Pol II structure and structure of the elongation complex.
Figure 4: EM structure of the Pol II–mediator complex.
Figure 5: Summary of human general transcription factor protein-DNA crosslinks at a promoter.
Figure 6: The Pol II–TFIIB complex and a model for the structure of the PIC.
Figure 7: EM structure of the Pol II–TFIIF complex.

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References

  1. Hampsey, M. Molecular genetics of the RNA polymerase II general transcriptional machinery. Microbiol. Mol. Biol. Rev. 62, 465– 503 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lee, T.I. & Young, R.A. Transcription of eukaryotic protein-coding genes. Annu. Rev. Genet. 34, 77– 137 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. Woychik, N.A. & Hampsey, M. The RNA polymerase II machinery: structure illuminates function. Cell 108, 453– 463 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Borukhov, S. & Nudler, E. RNA polymerase holoenzyme: structure, function and biological implications. Curr. Opin. Microbiol. 6, 93– 100 (2003).

    Article  CAS  PubMed  Google Scholar 

  5. Murakami, K.S. & Darst, S.A. Bacterial RNA polymerases: the wholo story. Curr. Opin. Struct. Biol. 13, 31– 39 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Chen, H.T. & Hahn, S. Binding of TFIIB to RNA polymerase II: mapping the binding site for the TFIIB zinc ribbon domain within the preinitiation complex. Mol. Cell 12, 437– 447 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. Chung, W.H. et al. RNA Polymerase II/TFIIF Structure and Conserved Organization of the Initiation Complex. Mol. Cell 12, 1003– 1013 (2003).

    Article  CAS  PubMed  Google Scholar 

  8. Bushnell, D.A., Westover, K.D., Davis, R.E. & Kornberg, R.D. Structural basis of transcription: an RNA polymerase II-TFIIB cocrystal at 4.5 Å. Science 303, 983– 988 (2004).

    Article  CAS  PubMed  Google Scholar 

  9. Bell, S.D. & Jackson, S.P. Transcription in Archaea. Cold Spring Harb. Symp. Quant. Biol. 63, 41– 51 (1998).

    Article  CAS  PubMed  Google Scholar 

  10. Ebright, R.H. RNA polymerase: structural similarities between bacterial RNA polymerase and eukaryotic RNA polymerase II. J. Mol. Biol. 304, 687– 698 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Schramm, L. & Hernandez, N. Recruitment of RNA polymerase III to its target promoters. Genes Dev. 16, 2593– 2620 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. Grummt, I. Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev. 17, 1691– 1702 (2003).

    Article  CAS  PubMed  Google Scholar 

  13. Ptashne, M. & Gann, A. Genes and Signals (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2002).

    Google Scholar 

  14. Cosma, M.P. Ordered recruitment: gene-specific mechanism of transcription activation. Mol. Cell 10, 227– 236 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Wang, W., Carey, M. & Gralla, J.D. Polymerase II promoter activation: closed complex formation and ATP-driven start site opening. Science 255, 450– 453 (1992).

    Article  CAS  PubMed  Google Scholar 

  16. Luse, D.S. & Jacob, G.A. Abortive initiation by RNA polymerase II in vitro at the adenovirus 2 major late promoter. J. Biol. Chem. 262, 14990– 14997 (1987).

    Article  CAS  PubMed  Google Scholar 

  17. Holstege, F.C.P., Fiedler, U. & Timmers, H.T.M. Three transitions in the RNA polymerase II transcription complex during initiation. EMBO J. 16, 7468– 7480 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bentley, D. The mRNA assembly line: transcription and processing machines in the same factory. Curr. Opin. Cell Biol. 14, 336– 342 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Yudkovsky, N., Ranish, J.A. & Hahn, S. A transcription reinitiation intermediate that is stabilized by activator. Nature 408, 225– 229 (2000).

    Article  CAS  PubMed  Google Scholar 

  20. Smale, S.T. & Kadonaga, J.T. The RNA polymerase II core promoter. Annu. Rev. Biochem. 72, 449– 479 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Kim, Y., Geiger, J.H., Hahn, S. & Sigler, P.B. Crystal structure of a yeast TBP/TATA-box complex. Nature 365, 512– 520 (1993).

    Article  CAS  PubMed  Google Scholar 

  22. Kim, J.L., Nikolov, D.B. & Burley, S.K. Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature 365, 520– 527 (1993).

    Article  CAS  PubMed  Google Scholar 

  23. Cox, J.M. et al. Bidirectional binding of the TATA box binding protein to the TATA box. Proc. Natl. Acad. Sci. USA 94, 13475– 13480 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lagrange, T., Kapanidis, A.N., Tang, H., Reinberg, D. & Ebright, R.H. New core promoter element in RNA polymerase II-dependent transcription: sequence-specific DNA binding by transcription factor IIB. Genes Dev. 12, 34– 44 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Qureshi, S.A. & Jackson, S.P. Sequence-specific DNA binding by the S. shibatae TFIIB homolog, TFB, and its effect on promoter strength. Mol. Cell 1, 389– 400 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Bell, S.D., Kosa, P.L., Sigler, P.B. & Jackson, S.P. Orientation of the transcription preinitiation complex in archaea. Proc. Natl. Acad. Sci. USA 96, 13662– 13667 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Littlefield, O., Korkhin, Y. & Sigler, P.B. The structural basis for the oriented assembly of a TBP/TFB/promoter complex. Proc. Natl. Acad. Sci. USA 96, 13668– 13673 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chalkley, G.E. & Verrijzer, C.P. DNA binding site selection by RNA polymerase II TAFs: a TAF(II)250–TAF(II)150 complex recognizes the initiator. EMBO J. 18, 4835– 4845 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Oelgeschlager, T., Chiang, C.-M. & Roeder, R.G. Topology and reorganization of a human TFIID-promoter complex. Nature 382, 735– 738 (1996).

    Article  CAS  PubMed  Google Scholar 

  30. Burke, T.W. & Kadonaga, J.T. The downstream core promoter element, DPE, is conserved from Drosophila to humans and is recognized by TAFII60 of Drosophila. Genes Dev. 11, 3020– 3031 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Butler, J.E. & Kadonaga, J.T. Enhancer-promoter specificity mediated by DPE or TATA core promoter motifs. Genes Dev. 15, 2515– 2519 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ohler, U., Liao, G.C., Niemann, H. & Rubin, G.M. Computational analysis of core promoters in the Drosophila genome. Genome Biol. 3, 0087.1– 0087.12 (2002).

    Article  Google Scholar 

  33. Patikoglou, G.A. et al. TATA element recognition by the TATA box-binding protein has been conserved throughout evolution. Genes Dev. 13, 3217– 3230 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wobbe, C.R. & Struhl, K. Yeast and human TATA-binding proteins have nearly identical DNA sequence requirements for transcription in vitro. Mol. Cell. Biol. 10, 3859– 3867 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Ranish, J.A., Yudkovsky, N. & Hahn, S. Intermediates in formation and activity of the RNA polymerase II preinitiation complex: holoenzyme recruitment and a postrecruitment role for the TATA box and TFIIB. Genes Dev. 13, 49– 63 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Martinez, E. et al. Core promoter-specific function of a mutant transcription factor TFIID defective in TATA-box binding. Proc. Natl. Acad. Sci. USA 92, 11864– 11868 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hochheimer, A. & Tjian, R. Diversified transcription initiation complexes expand promoter selectivity and tissue-specific gene expression. Genes Dev. 17, 1309– 1320 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Davidson, I. The genetics of TBP and TBP-related factors. Trends Biochem. Sci. 28, 391– 398 (2003).

    Article  CAS  PubMed  Google Scholar 

  39. Holmes, M.C. & Tjian, R. Promoter-selective properties of the TBP-related factor TRF1. Science 288, 867– 870 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Takada, S., Lis, J.T., Zhou, S. & Tjian, R. A TRF1:BRF complex directs Drosophila RNA polymerase III transcription. Cell 101, 459– 469 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Nikolov, D.B. et al. Crystal structure of a TFIIB-TBP-TATA-element ternary complex. Nature 377, 119– 128 (1995).

    Article  CAS  PubMed  Google Scholar 

  42. Geiger, J.H., Hahn, S., Lee, S. & Sigler, P.B. Crystal structure of the yeast TFIIA/TBP/DNA complex. Science 272, 830– 836 (1996).

    Article  CAS  PubMed  Google Scholar 

  43. Tan, S., Hunziker, Y., Sargent, D.F. & Richmond, T.J. Crystal structure of a yeast TFIIA/TBP/DNA complex. Nature 381, 127– 134 (1996).

    Article  CAS  PubMed  Google Scholar 

  44. Weideman, C.A. et al. Dynamic interplay of TFIIA, TBP, and TATA DNA. J. Mol. Biol. 271, 61– 75 (1997).

    Article  CAS  PubMed  Google Scholar 

  45. Kokubo, T., Swanson, M.J., Nishikawa, J.I., Hinnebusch, A.G. & Nakatani, Y. The yeast TAF145 inhibitory domain and TFIIA competitively bind to TATA-binding protein. Mol. Cell. Biol. 18, 1003– 1012 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Liu, D. et al. Solution structure of a TBP-TAF(II)230 complex: protein mimicry of the minor groove surface of the TATA box unwound by TBP. Cell 94, 573– 583 (1998).

    Article  CAS  PubMed  Google Scholar 

  47. Sanders, S.L., Garbett, K.A. & Weil, P.A. Molecular characterization of Saccharomyces cerevisiae TFIID. Mol. Cell. Biol. 22, 6000– 6013 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Chi, T., Lieberman, P., Ellwood, K. & Carey, M. A general mechanism for transcriptional synergy by eukaryotic activators. Nature 377, 254– 257 (1995).

    Article  CAS  PubMed  Google Scholar 

  49. Pardee, T.S., Bangur, C.S. & Ponticelli, A.S. The N-terminal region of yeast TFIIB contains two adjacent functional domains involved in stable RNA polymerase II binding and transcription start site selection. J. Biol. Chem. 273, 17859– 17864 (1998).

    Article  CAS  PubMed  Google Scholar 

  50. Hahn, S. & Roberts, S. The zinc ribbon domains of the general transcription factors TFIIB and Brf: conserved functional surfaces but different roles in transcription initiation. Genes Dev. 14, 719– 730 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Albright, S.R. & Tjian, R. TAFs revisited: more data reveal new twists and confirm old ideas. Gene 242, 1– 13 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Green, M.R. TBP-associated factors (TAFIIs): multiple, selective transcriptional mediators in common complexes. Trends Biochem. Sci. 25, 59– 63 (2000).

    Article  CAS  PubMed  Google Scholar 

  53. Tora, L. A unified nomenclature for TATA box binding protein (TBP)-associated factors (TAFs) involved in RNA polymerase II transcription. Genes Dev. 16, 673– 675 (2002).

    Article  CAS  PubMed  Google Scholar 

  54. Chen, J.-L., Attardi, L.D., Verrijzer, C.P., Yokomori, K. & Tjian, R. Assembly of recombinant TFIID reveals differential coactivator requirements for distinct transcriptional activators. Cell 79, 93– 105 (1994).

    Article  CAS  PubMed  Google Scholar 

  55. Thut, C.J., Chen, J.L., Klemm, R. & Tjian, R. p53 transcriptional activation mediated by coactivators TAFII40 and TAFII60. Science 267, 100– 104 (1995).

    Article  CAS  PubMed  Google Scholar 

  56. Wassarman, D.A. & Sauer, F. TAF(II)250: a transcription toolbox. J. Cell Sci. 114, 2895– 2902 (2001).

    Article  CAS  PubMed  Google Scholar 

  57. Andel, F. 3rd, Ladurner, A.G., Inouye, C., Tjian, R. & Nogales, E. Three-dimensional structure of the human TFIID-IIA-IIB complex. Science 286, 2153– 2156 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. Brand, M., Leurent, C., Mallouh, V., Tora, L. & Schultz, P. Three-dimensional structures of the TAFII-containing complexes TFIID and TFTC. Science 286, 2151– 2153 (1999).

    Article  CAS  PubMed  Google Scholar 

  59. Xie, X. et al. Structural similarity between TAFs and the heterotetrameric core of the histone octamer. Nature 380, 316– 322 (1996).

    Article  CAS  PubMed  Google Scholar 

  60. Werten, S. et al. Crystal structure of a subcomplex of human transcription factor TFIID formed by TATA binding protein-associated factors hTAF4 (hTAF(II)135) and hTAF12 (hTAF(II)20). J. Biol. Chem. 277, 45502– 45509 (2002).

    Article  CAS  PubMed  Google Scholar 

  61. Gangloff, Y.G., Romier, C., Thuault, S., Werten, S. & Davidson, I. The histone fold is a key structural motif of transcription factor TFIID. Trends Biochem. Sci. 26, 250– 257 (2001).

    Article  CAS  PubMed  Google Scholar 

  62. Leurent, C. et al. Mapping histone fold TAFs within yeast TFIID. EMBO J. 21, 3424– 3433 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F. & Richmond, T.J. Crystal structure of the nucleosome core particle at 2.9Å resolution. Nature 389, 251– 260 (1997).

    Article  CAS  PubMed  Google Scholar 

  64. Freiman, R.N. et al. Requirement of tissue-selective TBP-associated factor TAFII105 in ovarian development. Science 293, 2084– 2087 (2001).

    Article  CAS  PubMed  Google Scholar 

  65. Hiller, M.A., Lin, T.Y., Wood, C. & Fuller, M.T. Developmental regulation of transcription by a tissue-specific TAF homolog. Genes Dev. 15, 1021– 1030 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Shen, W.C. et al. Systematic analysis of essential yeast TAFs in genome-wide transcription and preinitiation complex assembly. EMBO J. 22, 3395– 3402 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kuras, L., Kosa, P., Mencia, M. & Struhl, K. TAF-containing and TAF-independent forms of transcriptionally active TBP in vivo. Science 288, 1244– 1248 (2000).

    Article  CAS  PubMed  Google Scholar 

  68. Li, X.Y., Bhaumik, S.R. & Green, M.R. Distinct classes of yeast promoters revealed by differential TAF recruitment. Science 288, 1242– 1244 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Lee, T.I. et al. Redundant roles for the TFIID and SAGA complexes in global transcription. Nature 405, 701– 704 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. Zhang, G. et al. Crystal structure of Thermus aquaticus core RNA polymerase at 3.3 Å resolution. Cell 98, 811– 824 (1999).

    Article  CAS  PubMed  Google Scholar 

  71. Cramer, P. et al. Architecture of RNA polymerase II and implications for the transcription mechanism. Science 288, 640– 649 (2000).

    Article  CAS  PubMed  Google Scholar 

  72. Cramer, P., Bushnell, D.A. & Kornberg, R.D. Structural basis of transcription: RNA polymerase II at 2.8 Å resolution. Science 292, 1863– 1876 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Opalka, N. et al. Structure and function of the transcription elongation factor GreB bound to bacterial RNA polymerase. Cell 114, 335– 345 (2003).

    Article  CAS  PubMed  Google Scholar 

  74. Mekler, V. et al. Structural organization of bacterial RNA polymerase holoenzyme and the RNA polymerase-promoter open complex. Cell 108, 599– 614 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Murakami, K.S., Masuda, S. & Darst, S.A. Structural basis of transcription initiation: RNA polymerase holoenzyme at 4 Å resolution. Science 296, 1280– 1284 (2002).

    Article  CAS  PubMed  Google Scholar 

  76. Vassylyev, D.G. et al. Crystal structure of a bacterial RNA polymerase holoenzyme at 2.6 Å resolution. Nature 417, 712– 719 (2002).

    Article  CAS  PubMed  Google Scholar 

  77. Murakami, K.S., Masuda, S., Campbell, E.A., Muzzin, O. & Darst, S.A. Structural basis of transcription initiation: an RNA polymerase holoenzyme-DNA complex. Science 296, 1285– 1290 (2002).

    Article  CAS  PubMed  Google Scholar 

  78. Armache, K.J., Kettenberger, H. & Cramer, P. Architecture of initiation-competent 12-subunit RNA polymerase II. Proc. Natl. Acad. Sci. USA 100, 6964– 6968 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Bushnell, D.A. & Kornberg, R.D. Complete, 12-subunit RNA polymerase II at 4.1-Å resolution: implications for the initiation of transcription. Proc. Natl. Acad. Sci. USA 100, 6969– 6973 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Gnatt, A.L., Cramer, P., Fu, J., Bushnell, D.A. & Kornberg, R.D. Structural basis of transcription: an RNA polymerase II elongation complex at 3.3 Å resolution. Science 292, 1876– 1882 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. Westover, K.D., Bushnell, D.A. & Kornberg, R.D. Structural basis of transcription: separation of RNA from DNA by RNA polymerase II. Science 303, 1014– 1016 (2004).

    Article  CAS  PubMed  Google Scholar 

  82. Kettenberger, H., Armache, K.J. & Cramer, P. Architecture of the RNA polymerase II–TFIIS complex and implications for mRNA cleavage. Cell 114, 347– 357 (2003).

    Article  CAS  PubMed  Google Scholar 

  83. Davis, J.A., Takagi, Y., Kornberg, R.D. & Asturias, F.A. Structure of the yeast RNA polymerase II holoenzyme: mediator conformation and polymerase interaction. Mol. Cell 10, 409– 415 (2002).

    Article  CAS  PubMed  Google Scholar 

  84. Liu, Y. et al. Two cyclin-dependent kinases promote RNA polymerase II transcription and formation of the scaffold complex. Mol. Cell. Biol. 24, 1721– 1735 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ahn, S.H., Kim, M. & Buratowski, S. Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain couples transcription and 3′ end processing. Mol. Cell 13, 67– 76 (2004).

    Article  CAS  PubMed  Google Scholar 

  86. Verdecia, M.A., Bowman, M.E., Lu, K.P., Hunter, T. & Noel, J.P. Structural basis for phosphoserine-proline recognition by group IV WW domains. Nat. Struct. Biol. 7, 639– 643 (2000).

    Article  CAS  PubMed  Google Scholar 

  87. Fabrega, C., Shen, V., Shuman, S. & Lima, C.D. Structure of an mRNA capping enzyme bound to the phosphorylated carboxy-terminal domain of RNA polymerase II. Mol. Cell 11, 1549– 1561 (2003).

    Article  CAS  PubMed  Google Scholar 

  88. Hope, I.A., Mahadevan, S. & Struhl, K. Structural and functional characterization of the short acidic transcriptional activation region of yeast GCN4 protein. Nature 333, 635– 640 (1988).

    Article  CAS  PubMed  Google Scholar 

  89. Cress, W.D. & Triezenberg, S.J. Critical structural elements of the VP16 transcriptional activation domain. Science 251, 87– 90 (1991).

    Article  CAS  PubMed  Google Scholar 

  90. Jackson, B.M., Drysdale, C.M., Natarajan, K. & Hinnebusch, A.G. Identification of seven hydrophobic clusters in GCN4 making redundant contributions to transcriptional activation. Mol. Cell. Biol. 16, 5557– 5571 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Malik, S. & Roeder, R.G. Transcriptional regulation through mediator-like coactivators in yeast and metazoan cells. Trends Biochem. Sci. 25, 277– 283 (2000).

    Article  CAS  PubMed  Google Scholar 

  92. Boube, M., Joulia, L., Cribbs, D.L. & Bourbon, H.M. Evidence for a mediator of RNA polymerase II transcriptional regulation conserved from yeast to man. Cell 110, 143– 151 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Cosma, M.P., Tanaka, T. & Nasmyth, K. Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter. Cell 97, 299– 311 (1999).

    Article  CAS  PubMed  Google Scholar 

  94. Rani, P.G., Ranish, J.A. & Hahn, S. RNA polymerase II (Pol II)-TFIIF and Pol II-mediator complexes: the major stable Pol II complexes and their activity in transcription initiation and reinitiation. Mol. Cell. Biol. 24, 1709– 1720 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Kang, J.S. et al. The structural and functional organization of the yeast mediator complex. J. Biol. Chem. 276, 42003– 42010 (2001).

    Article  CAS  PubMed  Google Scholar 

  96. Forget, D. et al. RAP74 induces promoter contacts by RNA polymerase II upstream and downstream of a DNA bend centered on the TATA box. Proc. Natl. Acad. Sci. USA 94, 7150– 7155 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kim, T.-K. et al. Trajectory of DNA in the RNA polymerase II transcription preinitiation complex. Proc. Natl. Acad. Sci. USA 94, 12268– 12273 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Kim, T.K., Ebright, R.H. & Reinberg, D. Mechanism of ATP-dependent promoter melting by transcription factor IIH. Science 288, 1418– 1422 (2000).

    Article  CAS  PubMed  Google Scholar 

  99. Forget, D., Langelier, M.-F., Therien, C., Trinh, V. & Coulombe, B. Photo-cross-linking of a purified preinitiation complex reveals central roles for the RNA polymerase II mobile clamp and TFIIE in initiation mechanisms. Mol. Cell. Biol. 24, 1122– 1131 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bartlett, M.S., Thomm, M. & Geiduschek, E.P. Topography of the euryarchaeal transcription initiation complex. J. Biol. Chem. 279, 5894– 5903 (2004).

    Article  CAS  PubMed  Google Scholar 

  101. Renfrow, M.B. et al. Transcription factor B contacts promoter DNA near the transcription start site of the archaeal transcription initiation complex. J. Biol. Chem. 279, 2825– 2831 (2004).

    Article  CAS  PubMed  Google Scholar 

  102. Gaiser, F., Tan, S. & Richmond, T.J. Novel dimerization fold of RAP30/RAP74 in human TFIIF at 1.7 Å resolution. J. Mol. Biol. 302, 1119– 1127 (2000).

    Article  CAS  PubMed  Google Scholar 

  103. Kamada, K., Roeder, R.G. & Burley, S.K. Molecular mechanism of recruitment of TFIIF-associating RNA polymerase C-terminal domain phosphatase (FCP1) by transcription factor IIF. Proc. Natl. Acad. Sci. USA 100, 2296– 2299 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Nguyen, B.D. et al. NMR structure of a complex containing the TFIIF subunit RAP74 and the RNA polymerase II carboxyl-terminal domain phosphatase FCP1. Proc. Natl. Acad. Sci. USA 100, 5688– 5693 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Sopta, M., Burton, Z.F. & Greenblatt, J. Structure and associated DNA-helicase activity of a general transcription initiation factor that binds to RNA polymerase II. Nature 341, 410– 414 (1989).

    Article  CAS  PubMed  Google Scholar 

  106. Henry, N.L. et al. TFIIF-TAF-RNA polymerase II connection. Genes Dev. 8, 2868– 2878 (1994).

    Article  CAS  PubMed  Google Scholar 

  107. Bushnell, D.A., Bamdad, C. & Kornberg, R.D. A minimal set of RNA Pol II transcription protein interactions. J. Biol. Chem. 271, 20170– 20174 (1996).

    Article  CAS  PubMed  Google Scholar 

  108. Ohkuma, Y. Multiple functions of general transcription factors TFIIE and TFIIH in transcription: possible points of regulation by trans-acting factors. J. Biochem. 122, 481– 489 (1997).

    Article  CAS  PubMed  Google Scholar 

  109. Sayre, M.H., Tschochner, H. & Kornberg, R.D. Purification and properties of S. cerevisiae RNA polymerase II general initiation factor a. J. Biol. Chem. 267, 23383– 23387 (1992).

    Article  CAS  PubMed  Google Scholar 

  110. Leuther, K.K., Bushnell, D.A. & Kornberg, R.D. Two-dimensional crystallography of TFIIB- and IIE-RNA polymerase II complexes: implications for start site selection and initiation complex formation. Cell 85, 773– 779 (1996).

    Article  CAS  PubMed  Google Scholar 

  111. Okuda, M. et al. Structure of the central core domain of TFIIEβ with a novel double-stranded DNA-binding surface. EMBO J. 19, 1346– 1356 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Coin, F. & Egly, J.M. Ten years of TFIIH. Cold Spring Harb. Symp. Quant. Biol. 63, 105– 110 (1998).

    Article  CAS  PubMed  Google Scholar 

  113. Takagi, Y. et al. Revised subunit structure of yeast TFIIH and reconciliation with human TFIIH. J. Biol. Chem. 278, 43897– 43900 (2003).

    Article  CAS  PubMed  Google Scholar 

  114. Dubaele, S. et al. Basal transcription defect discriminates between xeroderma pigmentosum and trichothiodystrophy in XPD patients. Mol. Cell 11, 1635– 1646 (2003).

    Article  CAS  PubMed  Google Scholar 

  115. Schultz, P. et al. Molecular structure of human TFIIH. Cell 102, 599– 607 (2000).

    Article  CAS  PubMed  Google Scholar 

  116. Chang, W.H. & Kornberg, R.D. Electron crystal structure of the transcription factor and DNA repair complex, core TFIIH. Cell 102, 609– 613 (2000).

    Article  CAS  PubMed  Google Scholar 

  117. Caruthers, J.M. & McKay, D.B. Helicase structure and mechanism. Curr. Opin. Struct. Biol. 12, 123– 133 (2002).

    Article  CAS  PubMed  Google Scholar 

  118. Choi, W.S., Yan, M., Nusinow, D. & Gralla, J.D. In vitro transcription and start site selection in Schizosaccharomyces pombe. J. Mol. Biol. 319, 1005– 1013 (2002).

    Article  CAS  PubMed  Google Scholar 

  119. Hekmatpanah, D.S. & Young, R.A. Mutations in a conserved region of RNA polymerase II influence the accuracy of mRNA start site selection. Mol. Cell. Biol. 11, 5781– 5791 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Berroteran, R.W., Ware, D.E. & Hampsey, M. The sua8 suppressors of S. cerevisiae encode replacements of conserved residues within the largest subunit of RNA polymerase II and affect transcription start site selection similarly to sua7 (TFIIB) mutations. Mol. Cell. Biol. 14, 226– 237 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Pinto, I., Ware, D.E. & Hampsey, M. The yeast SUA7 gene encodes a homolog of human transcription factor TFIIB and is required for normal start site selection in vivo. Cell 68, 977– 988 (1992).

    Article  CAS  PubMed  Google Scholar 

  122. Faitar, S.L., Brodie, S.A. & Ponticelli, A.S. Promoter-specific shifts in transcription initiation conferred by yeast TFIIB mutations are determined by the sequence in the immediate vicinity of the start sites. Mol. Cell. Biol. 21, 4427– 4440 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Sun, Z.W., Tessmer, A. & Hampsey, M. Functional interaction between TFIIB and the Rpb9 (Ssu73) subunit of RNA polymerase II in Saccharomyces cerevisiae. Nucleic Acids Res. 24, 2560– 2566 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Giardina, C. & Lis, J.T. DNA melting on yeast RNA polymerase II promoters. Science 261, 759– 762 (1993).

    Article  CAS  PubMed  Google Scholar 

  125. Chen, H.T., Legault, P., Glushka, J., Omichinski, J.G. & Scott, R.A. Structure of a (Cys3His) zinc ribbon, a ubiquitous motif in archaeal and eucaryal transcription. Protein Sci. 9, 1743– 1752 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Bushnell, D.A., Cramer, P. & Kornberg, R.D. Structural basis of transcription: α-amanitin-RNA polymerase II cocrystal at 2.8 Å resolution. Proc. Natl. Acad. Sci. USA 99, 1218– 1222 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Douziech, M. et al. Mechanism of promoter melting by the xeroderma pigmentosum complementation group B helicase of transcription factor IIH revealed by protein-DNA photo-cross-linking. Mol. Cell. Biol. 20, 8168– 8177 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

I thank D. Bushnell, R. Kornberg, and F. Asturias for figures and for communication of results before publication, E. Nogales for figures, B. Moorefield and H.-T. Chen for their comments on the manuscript and H.-T. Chen for discussions and help with figures. This work was supported by a grant from the US National Institutes of Health. S.H. is an associate investigator of the Howard Hughes Medical Institute.

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Hahn, S. Structure and mechanism of the RNA polymerase II transcription machinery. Nat Struct Mol Biol 11, 394–403 (2004). https://doi.org/10.1038/nsmb763

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