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Molecular insight into RNA polymerase I promoter recognition and promoter melting

Yashar Sadian, Florence Baudin, Lucas Tafur, Brice Murciano, Rene Wetzel, Felix Weis and Christoph W. Müller ()
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Yashar Sadian: Structural and Computational Biology Unit
Florence Baudin: Structural and Computational Biology Unit
Lucas Tafur: Structural and Computational Biology Unit
Brice Murciano: Structural and Computational Biology Unit
Rene Wetzel: Structural and Computational Biology Unit
Felix Weis: Structural and Computational Biology Unit
Christoph W. Müller: Structural and Computational Biology Unit

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract RNA polymerase I (Pol I) assembles with core factor (CF) and Rrn3 on the rDNA core promoter for transcription initiation. Here, we report cryo-EM structures of closed, intermediate and open Pol I initiation complexes from 2.7 to 3.7 Å resolution to visualize Pol I promoter melting and to structurally and biochemically characterize the recognition mechanism of Pol I promoter DNA. In the closed complex, double-stranded DNA runs outside the DNA-binding cleft. Rotation of CF and upstream DNA with respect to Pol I and Rrn3 results in the spontaneous loading and opening of the promoter followed by cleft closure and positioning of the Pol I A49 tandem winged helix domain (tWH) onto DNA. Conformational rearrangement of A49 tWH leads to a clash with Rrn3 to initiate complex disassembly and promoter escape. Comprehensive insight into the Pol I transcription initiation cycle allows comparisons with promoter opening by Pol II and Pol III.

Date: 2019
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DOI: 10.1038/s41467-019-13510-w

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