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Structural Basis of RNA Polymerase I Transcription Initiation
- Engel, Christoph, Gubbey, Tobias, Neyer, Simon, Sainsbury, Sarah, Oberthuer, Christiane, Baejen, Carlo, Bernecky, Carrie, Cramer, Patrick
- Cell 2017 v.169 no.1 pp. 120-131.e22
- DNA, DNA-directed RNA polymerase, X-ray diffraction, cryo-electron microscopy, promoter regions, ribosomal RNA
- Transcription initiation at the ribosomal RNA promoter requires RNA polymerase (Pol) I and the initiation factors Rrn3 and core factor (CF). Here, we combine X-ray crystallography and cryo-electron microscopy (cryo-EM) to obtain a molecular model for basal Pol I initiation. The three-subunit CF binds upstream promoter DNA, docks to the Pol I-Rrn3 complex, and loads DNA into the expanded active center cleft of the polymerase. DNA unwinding between the Pol I protrusion and clamp domains enables cleft contraction, resulting in an active Pol I conformation and RNA synthesis. Comparison with the Pol II system suggests that promoter specificity relies on a distinct “bendability” and “meltability” of the promoter sequence that enables contacts between initiation factors, DNA, and polymerase.