9J0N

Paused elongation complex of mammalian RNA polymerase II with nucleosome (PEC2-nuc)

9J0N の概要

• エントリーDOI: 10.2210/pdb9j0n/pdb
• EMDBエントリー: 61058
• 分子名称: DNA-directed RNA polymerase subunit, Transcription elongation factor SPT5, Non-template DNA (157-MER), ... (28 entities in total)
• 機能のキーワード: rna polymerase, nelf, nucleosome, dna, rna, tfiis, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 30
• 化学式量合計: 1171165.15

構造登録者

Naganuma, M.,Kujirai, T.,Ehara, H.,Uejima, T.,Ito, T.,Goto, M.,Aoki, M.,Henmi, M.,Miyamoto-Kohno, S.,Shirouzu, M.,Kurumizaka, H.,Sekine, S. (登録日: 2024-08-02, 公開日: 2025-02-05, 最終更新日: 2025-06-18)

主引用文献

Naganuma, M.,Kujirai, T.,Ehara, H.,Uejima, T.,Ito, T.,Goto, M.,Aoki, M.,Henmi, M.,Miyamoto-Kohno, S.,Shirouzu, M.,Kurumizaka, H.,Sekine, S.I.
Structural insights into promoter-proximal pausing of RNA polymerase II at +1 nucleosome.
Sci Adv, 11:eadu0577-eadu0577, 2025

PubMed Abstract: The metazoan transcription elongation complex (EC) of RNA polymerase II (RNAPII) generally stalls between the transcription start site and the first (+1) nucleosome. This promoter-proximal pausing involves negative elongation factor (NELF), 5,6-dichloro-1-β-d-ribobenzimidazole sensitivity-inducing factor (DSIF), and transcription elongation factor IIS (TFIIS) and is critical for subsequent productive transcription elongation. However, the detailed pausing mechanism and the involvement of the +1 nucleosome remain enigmatic. Here, we report cryo-electron microscopy structures of ECs stalled on nucleosomal DNA. In the absence of TFIIS, the EC is backtracked/arrested due to conflicts between NELF and the nucleosome. We identified two alternative binding modes of NELF, one of which reveals a critical contact with the downstream DNA through the conserved NELF-E basic helix. Upon binding with TFIIS, the EC progressed to the nucleosome to establish a paused EC with a partially unwrapped nucleosome. This paused EC strongly restricts EC progression further downstream. These structures illuminate the mechanism of RNAPII pausing/stalling at the +1 nucleosome.

PubMed: 40043114
DOI: 10.1126/sciadv.adu0577

実験手法

ELECTRON MICROSCOPY (3.4 Å)