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Pilsl, Michael ; Engel, Christoph

Structural basis of RNA polymerase I pre-initiation complex formation and promoter melting

Pilsl, Michael and Engel, Christoph (2020) Structural basis of RNA polymerase I pre-initiation complex formation and promoter melting. Nature Communications 11 (1), pp. 1-10.

Date of publication of this fulltext: 09 Apr 2020 16:33
Article
DOI to cite this document: 10.5283/epub.43056


Abstract

Transcription of the ribosomal RNA precursor by RNA polymerase (Pol) I is a prerequisite for the biosynthesis of ribosomes in eukaryotes. Compared to Pols II and III, the mechanisms underlying promoter recognition, initiation complex formation and DNA melting by Pol I substantially diverge. Here, we report the high-resolution cryo-EM reconstruction of a Pol I early initiation intermediate ...

Transcription of the ribosomal RNA precursor by RNA polymerase (Pol) I is a prerequisite for the biosynthesis of ribosomes in eukaryotes. Compared to Pols II and III, the mechanisms underlying promoter recognition, initiation complex formation and DNA melting by Pol I substantially diverge. Here, we report the high-resolution cryo-EM reconstruction of a Pol I early initiation intermediate assembled on a double-stranded promoter scaffold that prevents the establishment of downstream DNA contacts. Our analyses demonstrate how efficient promoter-backbone interaction is achieved by combined re-arrangements of flexible regions in the 'core factor' subunits Rrn7 and Rrn11. Furthermore, structure-function analysis illustrates how destabilization of the melted DNA region correlates with contraction of the polymerase cleft upon transcription activation, thereby combining promoter recruitment with DNA-melting. This suggests that molecular mechanisms and structural features of Pol I initiation have co-evolved to support the efficient melting, initial transcription and promoter clearance required for high-level rRNA synthesis. RNA polymerase I (Pol I) catalyses the transcription of ribosomal RNA precursors, and its transcription initiation mechanism differs from that of Pol II and Pol III. Here the authors present the cryo-EM structure of a trapped early intermediate stage of promoter-recruited Pol I, which reveals the interactions of the basal rDNA transcription machinery with the native promoter, and discuss the mechanistic implications.



Involved Institutions


Details

Item typeArticle
Journal or Publication TitleNature Communications
Publisher:Nature
Open Access Type:Gold (with APC)
Place of Publication:LONDON
Volume:11
Number of Issue or Book Chapter:1
Page Range:pp. 1-10
Date5 March 2020
InstitutionsBiology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie
Projects
Funded by: Deutsche Forschungsgemeinschaft (DFG) (394580547)
Identification Number
ValueType
10.1038/s41467-020-15052-yDOI
KeywordsUPSTREAM ACTIVATION FACTOR; TATA-BINDING PROTEIN; TRANSCRIPTION INITIATION; RIBOSOMAL DNA; MOLECULAR-STRUCTURES; ELONGATION COMPLEX; CRYSTAL-STRUCTURE; TIF-IA; YEAST; TFIIB;
Dewey Decimal Classification500 Science > 570 Life sciences
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgYes
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-430569
Item ID43056

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