Download MendeleyStructural insights into promoter-proximal pausing of RNA polymerase II at +1 nucleosome.
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.(2025) Sci Adv 11: eadu0577-eadu0577
- PubMed: 40043114
- DOI: https://doi.org/10.1126/sciadv.adu0577
- Primary Citation of Related Structures:
9J0N, 9J0O, 9J0P - 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-¦Â-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.
Organizational Affiliation:
RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
