8UHA

Structure of paused transcription complex Pol II-DSIF-NELF - tilted

Summary for 8UHA

• Entry DOI: 10.2210/pdb8uha/pdb
• EMDB information: 42267
• Descriptor: Negative elongation factor E, RNA polymerase Rpb4/RPC9 core domain-containing protein, DNA-directed RNA polymerase II subunit E, ... (23 entities in total)
• Functional Keywords: nucleic acids, transcription, rna polymerase ii, nelf, dsif, pausing, transcription-dna-rna complex, transcription/dna/rna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 21
• Total formula weight: 919181.93

Authors

Vos, S.M.,Su, B.G. (deposition date: 2023-10-08, release date: 2024-03-20, Last modification date: 2024-09-11)

Primary citation

Su, B.G.,Vos, S.M.
Distinct negative elongation factor conformations regulate RNA polymerase II promoter-proximal pausing.
Mol.Cell, 84:1243-, 2024

PubMed Abstract: Metazoan gene expression regulation involves pausing of RNA polymerase (Pol II) in the promoter-proximal region of genes and is stabilized by DSIF and NELF. Upon depletion of elongation factors, NELF appears to accompany elongating Pol II past pause sites; however, prior work indicates that NELF prevents Pol II elongation. Here, we report cryoelectron microscopy structures of Pol II-DSIF-NELF complexes with NELF in two distinct conformations corresponding to paused and poised states. The paused NELF state supports Pol II stalling, whereas the poised NELF state enables transcription elongation as it does not support a tilted RNA-DNA hybrid. Further, the poised NELF state can accommodate TFIIS binding to Pol II, allowing for Pol II reactivation at paused or backtracking sites. Finally, we observe that the NELF-A tentacle interacts with the RPB2 protrusion and is necessary for pausing. Our results define how NELF can support pausing, reactivation, and elongation by Pol II.

PubMed: 38401543
DOI: 10.1016/j.molcel.2024.01.023

Experimental method

ELECTRON MICROSCOPY (3.5 Å)