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Structure of an RNA polymerase II–RNA inhibitor complex elucidates transcription regulation by noncoding RNAs

Nature Structural & Molecular Biology volume 13, pages 44–48 (2006)Cite this article

Abstract

The noncoding RNA B2 and the RNA aptamer FC bind RNA polymerase (Pol) II and inhibit messenger RNA transcription initiation, but not elongation. We report the crystal structure of FC*, the central part of FC RNA, bound to Pol II. FC* RNA forms a double stem-loop structure in the Pol II active center cleft. B2 RNA may bind similarly, as it competes with FC* RNA for Pol II interaction. Both RNA inhibitors apparently prevent the downstream DNA duplex and the template single strand from entering the cleft after DNA melting and thus interfere with open-complex formation. Elongation is not inhibited, as nucleic acids prebound in the cleft would exclude the RNA inhibitors. The structure also indicates that A-form RNA could interact with Pol II similarly to a B-form DNA promoter, as suggested for the bacterial transcription inhibitor 6S RNA.

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Figure 1: Mapping of the minimal Pol II-binding motif in FC RNA.
Figure 2: FC* RNA structure and analysis of Pol II contacts.
Figure 3: Structure of the Pol II–FC* RNA complex.
Figure 4: Model of RNA inhibition.

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Acknowledgements

We thank C. Schulze-Briese and the staff of beamline X06SA at the Swiss Light Source for help. We thank O. Weichenrieder for advice on cloning and in vitro transcription of B2 RNA. M.F. and P.C. are supported by the Deutsche Forschungsgemeinschaft, the European Union and the Fonds der Chemischen Industrie.

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  1. Hubert Kettenberger

    Present address: Department of Molecular Structural Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany

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  1. Department of Chemistry and Biochemistry, Gene Center, University of Munich, Feodor-Lynen-Str. 25, Munich, 81377, Germany

    Hubert Kettenberger, Florian Brueckner & Patrick Cramer

  2. Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Straße 1, Bonn, 53121, Germany

    Alexander Eisenführ, Mirko Theis & Michael Famulok

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Correspondence to Michael Famulok or Patrick Cramer.

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Kettenberger, H., Eisenführ, A., Brueckner, F. et al. Structure of an RNA polymerase II–RNA inhibitor complex elucidates transcription regulation by noncoding RNAs. Nat Struct Mol Biol 13, 44–48 (2006). https://doi.org/10.1038/nsmb1032

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