title: Functional architecture of RNA polymerase I.
abstract: Synthesis of ribosomal RNA (rRNA) by RNA polymerase (Pol) I is the first step in ribosome biogenesis and a regulatory switch in eukaryotic cell growth. Here we report the 12 A cryo-electron microscopic structure for the complete 14-subunit yeast Pol I, a homology model for the core enzyme, and the crystal structure of the subcomplex A14/43. In the resulting hybrid structure of Pol I, A14/43, the clamp, and the dock domain contribute to a unique surface interacting with promoter-specific initiation factors. The Pol I-specific subunits A49 and A34.5 form a heterodimer near the enzyme funnel that acts as a built-in elongation factor and is related to the Pol II-associated factor TFIIF. In contrast to Pol II, Pol I has a strong intrinsic 3'-RNA cleavage activity, which requires the C-terminal domain of subunit A12.2 and, apparently, enables ribosomal RNA proofreading and 3'-end trimming.
authors.affiliation: Gene Center Munich and Center for Integrated Protein Science CIPSM, Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
authors.forename: Claus-D
authors.initials: CD
authors.lastname: Kuhn
authors.forename: Sebastian R
authors.initials: SR
authors.lastname: Geiger
authors.forename: Sonja
authors.initials: S
authors.lastname: Baumli
authors.forename: Marco
authors.initials: M
authors.lastname: Gartmann
authors.forename: Jochen
authors.initials: J
authors.lastname: Gerber
authors.forename: Stefan
authors.initials: S
authors.lastname: Jennebach
authors.forename: Thorsten
authors.initials: T
authors.lastname: Mielke
authors.forename: Herbert
authors.initials: H
authors.lastname: Tschochner
authors.forename: Roland
authors.initials: R
authors.lastname: Beckmann
authors.forename: Patrick
authors.initials: P
authors.lastname: Cramer
mesh_terms: D001665:Binding Sites; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D004256:DNA Polymerase I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D010445:Peptide Elongation Factors / Q000737:chemistry / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D019473:Transcription Factors, TFII / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D010445:Peptide Elongation Factors; D010448:Peptide Initiation Factors; D021122:Protein Subunits; D012335:RNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; D019473:Transcription Factors, TFII; D035602:Transcriptional Elongation Factors; C018648:transcription factor S-II; D004256:DNA Polymerase I; C083536:POL1 protein, S cerevisiae; C056604:transcription factor TFIIF