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Genes Dev. 2011 Oct 1;25(19):2093-105. doi: 10.1101/gad.17363311. Epub 2011 Sep 22.

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

Author information

1
Gene Center, Department of Biochemistry, Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, 81377 Munich, Germany.

Abstract

Cell growth is regulated during RNA polymerase (Pol) I transcription initiation by the conserved factor Rrn3/TIF-IA 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 phospho-mimetic 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.

PMID:
21940764
PMCID:
PMC3197207
DOI:
10.1101/gad.17363311
[Indexed for MEDLINE]
Free PMC Article

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