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Structural basis of SNAPc-dependent snRNA transcription initiation by RNA polymerase II

Rengachari, Srinivasan; Schilbach, Sandra; Kaliyappan, Thangavelu; Gouge, Jerome; Zumer, Kristina; Schwarz, Juliane; Urlaub, Henning; ... Cramer, Patrick; + view all (2022) Structural basis of SNAPc-dependent snRNA transcription initiation by RNA polymerase II. Nature Structural & Molecular Biology , 29 (12) pp. 1159-1169. 10.1038/s41594-022-00857-w. Green open access

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Abstract

RNA polymerase II (Pol II) carries out transcription of both protein-coding and non-coding genes. Whereas Pol II initiation at protein-coding genes has been studied in detail, Pol II initiation at non-coding genes, such as small nuclear RNA (snRNA) genes, is less well understood at the structural level. Here, we study Pol II initiation at snRNA gene promoters and show that the snRNA-activating protein complex (SNAPc) enables DNA opening and transcription initiation independent of TFIIE and TFIIH in vitro. We then resolve cryo-EM structures of the SNAPc-containing Pol IIpre-initiation complex (PIC) assembled on U1 and U5 snRNA promoters. The core of SNAPc binds two turns of DNA and recognizes the snRNA promoter-specific proximal sequence element (PSE), located upstream of the TATA box-binding protein TBP. Two extensions of SNAPc, called wing-1 and wing-2, bind TFIIA and TFIIB, respectively, explaining how SNAPc directs Pol II to snRNA promoters. Comparison of structures of closed and open promoter complexes elucidates TFIIH-independent DNA opening. These results provide the structural basis of Pol II initiation at non-coding RNA gene promoters.

Type: Article
Title: Structural basis of SNAPc-dependent snRNA transcription initiation by RNA polymerase II
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41594-022-00857-w
Publisher version: https://doi.org/10.1038/s41594-022-00857-w
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Cryoelectron microscopy, Transcription, Transcriptional regulatory elements
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10164803
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