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-Structure paper
| タイトル | Structural insights into promoter-proximal pausing of RNA polymerase II at +1 nucleosome. |
|---|---|
| ジャーナル・号・ページ | Sci Adv, Vol. 11, Issue 10, Page eadu0577, Year 2025 |
| 掲載日 | 2025年3月7日 |
著者 | Masahiro Naganuma / Tomoya Kujirai / Haruhiko Ehara / Tamami Uejima / Tomoko Ito / Mie Goto / Mari Aoki / Masami Henmi / Sayako Miyamoto-Kohno / Mikako Shirouzu / Hitoshi Kurumizaka / Shun-Ichi Sekine / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Sci Adv / PubMed:40043114 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.3 - 3.4 Å |
| 構造データ | EMDB-61058, PDB-9j0n: EMDB-61059, PDB-9j0o: EMDB-61060, PDB-9j0p: |
| 化合物 | ![]() ChemComp-ZN: ![]() ChemComp-MG: |
| 由来 |
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キーワード | TRANSCRIPTION / RNA polymerase / NELF / nucleosome / DNA / RNA / TFIIS |
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