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PreprintCited by 19Genomics and Chromatin DynamicsRNA Research and SplicingNuclear Structure and Function

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

Open access
Rengachari, Srinivasan, Schilbach, Sandra, Kaliyappan, Thangavelu, Gouge, Jerome, Zumer, Kristina, Schwarz, Juliane, Urlaub, Henning, Dienemann, Christian, Vannini, Alessandro, Cramer, Patrick·2022·Nature Structural & Molecular Biology
DOI 10.1101/2022.09.21.508861PMC PMC9758055

Preprint — published as 10.1038/s41594-022-00857-w

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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 not 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 II preinitiation 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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Metadata

Authors
Rengachari, S., Schilbach, S., Kaliyappan, T., Gouge, J., Zumer, K., Schwarz, J., Urlaub, H., Dienemann, C., Vannini, A., & Cramer, P.
Affiliations
  • Max Planck Society (DE)
  • Institute of Cancer Research (GB)
  • Universitätsmedizin Göttingen (DE)
Corresponding author
  • Vannini, Alessandro
  • Cramer, Patrick
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
openRxiv
Published
2022-09-21
Volume
29
Issue
12
Pages
1159-1169
ISSN
1545-9985 (ISSN-L)
DOI
10.1101/2022.09.21.508861
PMC
PMC9758055
OpenAlex
W4309933570
Cited by
19
References
1
Citations by year
2026: 2 · 2025: 5 · 2024: 6 · 2023: 6
FWCI
1.39
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Structural & Molecular Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (200818/Z/16/Z)
  • Cancer Research UK (C47547/A21536)
  • Deutsche Forschungsgemeinschaft (EXC 2067/1 39072994, EXC 2067, EXC 2067‐1, SFB 860)
  • Max-Planck-Gesellschaft
  • H2020 European Research Council (882357)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
RNA polymerase II, transcription initiation, small nuclear RNA genes, preinitiation complex, proximal sequence element, TATA-binding protein, TFIIA, TFIIB, cryo-EM structure
MeSH terms
Animals, DNA, RNA Polymerase II, RNA Polymerase III, RNA, Small Nuclear, Transcription Factors, Transcription, Genetic, TATA-Box Binding Protein

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