Molecular basis of Rrn3-regulated RNA polymerase I initiation and cell growth

Blattner, C.; Jennebach, S.; Herzog, F.; Mayer, A.; Cheung, A. C. M.; Witte, G.; Lorenzen, K.; Hopfner, K.-P.; Heck, A. J. R.; Aebersold, R.; Cramer, P.

doi:10.1101/gad.17363311

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Molecular basis of Rrn3-regulated RNA polymerase I initiation and cell growth

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Cramer, P.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

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Citation

Blattner, C., Jennebach, S., Herzog, F., Mayer, A., Cheung, A. C. M., Witte, G., et al. (2011). Molecular basis of Rrn3-regulated RNA polymerase I initiation and cell growth. Genes and Development, 25(19), 2093-2105. doi:10.1101/gad.17363311.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0015-7D74-5

Abstract

Cell growth is regulated during RNA polymerase (Pol) I transcription initiation by the conserved factor Rrn3/TIFIA in yeast/humans. Here we provide a structure–function analysis of Rrn3 based on a combination of structural biology with in vivo and in vitro functional assays. The Rrn3 crystal structure reveals a unique HEAT repeat fold and a surface serine patch. Phosphorylation of this patch represses human Pol I transcription, and a phosphomimetic patch mutation prevents Rrn3 binding to Pol I in vitro and reduces cell growth and Pol I gene occupancy in vivo. Cross-linking indicates that Rrn3 binds Pol I between its subcomplexes, AC40/19 and A14/43, which faces the serine patch. The corresponding region of Pol II binds the Mediator head that cooperates with transcription factor (TF) IIB. Consistent with this, the Rrn3-binding factor Rrn7 is predicted to be a TFIIB homolog. This reveals the molecular basis of Rrn3-regulated Pol I initiation and cell growth, and indicates a general architecture of eukaryotic transcription initiation complexes.