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Structural basis of RNA polymerase III transcription initiation

DOI: 10.1038/nature25441 DOI Help

Authors: Guillermo Abascal-palacios (The Institute of Cancer Research) , Ewan Phillip Ramsay (The Institute of Cancer Research) , Fabienne Beuron (The Institute of Cancer Research) , Edward Morris (The Institute of Cancer Research) , Alessandro Vannini (The Institute of Cancer Research)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature , VOL 553 , PAGES 301 - 306

State: Published (Approved)
Published: January 2018
Diamond Proposal Number(s): 15629 , 16599 , 166601

Abstract: RNA polymerase (Pol) III transcribes essential non-coding RNAs, including the entire pool of transfer RNAs, the 5S ribosomal RNA and the U6 spliceosomal RNA, and is often deregulated in cancer cells. The initiation of gene transcription by Pol III requires the activity of the transcription factor TFIIIB to form a transcriptionally active Pol III preinitiation complex (PIC). Here we present electron microscopy reconstructions of Pol III PICs at 3.4–4.0 Å and a reconstruction of unbound apo-Pol III at 3.1 Å. TFIIIB fully encircles the DNA and restructures Pol III. In particular, binding of the TFIIIB subunit Bdp1 rearranges the Pol III-specific subunits C37 and C34, thereby promoting DNA opening. The unwound DNA directly contacts both sides of the Pol III cleft. Topologically, the Pol III PIC resembles the Pol II PIC, whereas the Pol I PIC is more divergent. The structures presented unravel the molecular mechanisms underlying the first steps of Pol III transcription and also the general conserved mechanisms of gene transcription initiation.

Journal Keywords: Cryoelectron microscopy; DNA; DNA metabolism; RNA; Transcription

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios II-Titan Krios II at Diamond

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