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  Structure of paused transcription complex Pol II–DSIF–NELF.

Vos, S. M., Farnung, L., Urlaub, H., & Cramer, P. (2018). Structure of paused transcription complex Pol II–DSIF–NELF. Nature, 560(7720), 601-606. doi:10.1038/s41586-018-0442-2.

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 Creators:
Vos, S. M.1, Author           
Farnung, L.1, Author           
Urlaub, H.2, Author           
Cramer, P.1, Author           
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              
2Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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 Abstract: Metazoan gene regulation often involves the pausing of RNA polymerase II (Pol II) in the promoter-proximal region. Paused Pol II is stabilized by the protein complexes DRB sensitivity-inducing factor (DSIF) and negative elongation factor (NELF). Here we report the cryo-electron microscopy structure of a paused transcription elongation complex containing Sus scrofa Pol II and Homo sapiens DSIF and NELF at 3.2 Å resolution. The structure reveals a tilted DNA–RNA hybrid that impairs binding of the nucleoside triphosphate substrate. NELF binds the polymerase funnel, bridges two mobile polymerase modules, and contacts the trigger loop, thereby restraining Pol II mobility that is required for pause release. NELF prevents binding of the anti-pausing transcription elongation factor IIS (TFIIS). Additionally, NELF possesses two flexible ‘tentacles’ that can contact DSIF and exiting RNA. These results define the paused state of Pol II and provide the molecular basis for understanding the function of NELF during promoter-proximal gene regulation.

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Language(s): eng - English
 Dates: 2018-08-222018-08-30
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41586-018-0442-2
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Title: Nature
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Pages: - Volume / Issue: 560 (7720) Sequence Number: - Start / End Page: 601 - 606 Identifier: -