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Structural basis of transcription initiation by RNA polymerase II

Key Points

  • Gene transcription is the first step in the expression of the genome. The regulation of transcription underlies organism development and cell differentiation.

  • Transcription of eukaryotic protein-coding genes commences with the assembly of a conserved initiation complex, consisting of RNA polymerase II (Pol II) and the general transcription factors, at promoter DNA.

  • Understanding how transcription initiates requires knowledge of the 3D structure of the Pol II initiation complex and intermediates on the initiation pathway.

  • After two decades of research, the structural basis of transcription initiation is emerging. Many crystal structures of components of the initiation complex have been resolved, and structural information on Pol II complexes with general transcription factors has been obtained recently.

  • Available structural data outline how Pol II cooperates with the general transcription factors to bind to and open promoter DNA and to direct RNA synthesis and escape from promoters. In the future, the structures of other initiation factors, which are not yet known, should be determined and the dynamics of the transition from transcription initiation to elongation should be analysed.

Abstract

Transcription of eukaryotic protein-coding genes commences with the assembly of a conserved initiation complex, which consists of RNA polymerase II (Pol II) and the general transcription factors, at promoter DNA. After two decades of research, the structural basis of transcription initiation is emerging. Crystal structures of many components of the initiation complex have been resolved, and structural information on Pol II complexes with general transcription factors has recently been obtained. Although mechanistic details await elucidation, available data outline how Pol II cooperates with the general transcription factors to bind to and open promoter DNA, and how Pol II directs RNA synthesis and escapes from the promoter.

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Figure 1: Schematic of Pol II transcription initiation.
Figure 2: Architecture of the core Pol II initiation complex.
Figure 3: TFIIH and promoter opening.
Figure 4: TFIID and promoter specificity.

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Acknowledgements

The authors thank members of the Cramer laboratory for comments on the manuscript. The authors apologize to those whose work could not be discussed owing to space limitations.

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Sainsbury, S., Bernecky, C. & Cramer, P. Structural basis of transcription initiation by RNA polymerase II. Nat Rev Mol Cell Biol 16, 129–143 (2015). https://doi.org/10.1038/nrm3952

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