Pilsl, Michael and Engel, Christoph (2020) Structural basis of RNA polymerase I pre-initiation complex formation and promoter melting. NATURE COMMUNICATIONS, 11 (1). ISSN 2041-1723,
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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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | UPSTREAM ACTIVATION FACTOR; TATA-BINDING PROTEIN; TRANSCRIPTION INITIATION; RIBOSOMAL DNA; MOLECULAR-STRUCTURES; ELONGATION COMPLEX; CRYSTAL-STRUCTURE; TIF-IA; YEAST; TFIIB; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Mar 2021 09:07 |
| Last Modified: | 29 Mar 2021 09:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44957 |
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