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

Rengachari, S., Schilbach, S., Kaliyappan, T., Gouge, J., Zumer, K., Schwarz, J., et al. (2022). Structural basis of SNAPc-dependent snRNA transcription initiation by RNA polymerase II. Nature Structural and Molecular Biology, 29, 1159-1169. doi:10.1038/s41594-022-00857-w.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000C-4619-A Version Permalink: https://hdl.handle.net/21.11116/0000-000C-D5C7-3
Genre: Journal Article

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 Creators:
Rengachari, Srinivasan1, Author           
Schilbach, Sandra1, Author           
Kaliyappan, Thangavelu, Author
Gouge, Jerome, Author
Zumer, Kristina1, Author           
Schwarz, Juliane2, Author           
Urlaub, Henning2, Author           
Dienemann, Christian1, Author           
Vannini, Alessandro, Author
Cramer, Patrick1, Author                 
Affiliations:
1Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, Göttingen, DE, ou_3350224              
2Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350290              

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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.

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Language(s): eng - English
 Dates: 2022-11-242022-12
 Publication Status: Issued
 Pages: -
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41594-022-00857-w
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Project name : We thank present and past members of the Cramer laboratory for help and discussions. We thank F. Grabbe for purifying TBP, TFIIA, TFIIB, TFIIE, TFIIF and TFIIH. We thank C. Dienemann and S. Schilbach for input towards designing the engineered U5 promoter DNA. We thank C. Diederich for discussions about AlphaFold2. We thank C. Dienemann and U. Steuerwald for maintenance of the electron microscopy facility. S. R. was supported by a postdoctoral fellowship from Peter und Traudl Engelhorn Foundation. A. V. was supported by the Cancer Research UK Programme Foundation (CR-UK C47547/A21536) and a Wellcome Trust Investigator Award (200818/Z/16/Z). H. U. was supported by the Deutsche Forschungsgemeinschaft (SFB860). P. C. was supported by the Deutsche Forschungsgemeinschaft (EXC 2067/1 39072994, SFB860) and the ERC Advanced Investigator Grant CHROMATRANS (grant agreement No. 882357).
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Project name : CHROMATRANS
Grant ID : 882357
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

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Title: Nature Structural and Molecular Biology
  Other : Nature Struct Biol
Source Genre: Journal
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Publ. Info: New York, NY : Nature Pub. Group
Pages: - Volume / Issue: 29 Sequence Number: - Start / End Page: 1159 - 1169 Identifier: ISSN: 1545-9993
CoNE: https://pure.mpg.de/cone/journals/resource/954925603763