对RNA聚合酶II在1+1核细胞组中的促进子-近端暂停的结构性见解
Masahiro Naganuma1, Tomoya Kujirai1,2, Haruhiko Ehara1
1RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
Science advances
|March 5, 2025
概括
RNA聚合酶II (RNAPII) 在+1核素中暂停涉及负延长因子 (NELF) 和核素之间的冲突. 通过TFIIS结合,RNAPII可以进化,形成一个暂停的复合体,限制进一步的延长.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 遗传学 是一个
背景情况:
- 促进 RNA 聚合酶 II (RNAPII) 的近端暂停是基因表达的关键调节步骤.
- 转录延长复合体 (EC) 在第一个 (+1) 核酶体之前停滞不前,涉及NELF,DSIF和TFIIS等因素.
- 暂停 +1 核酶的确切机制和 TFIIS 的作用仍然不清楚.
研究的目的:
- 为了阐明RNAPII在+1核素组中暂停的基础结构机制.
- 调查NELF和TFIIS在监管EC停滞和进展中的作用.
- 提供高分辨率的结构洞察力,了解暂停的EC-核体相互作用.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定核细胞DNA上停滞不前的EC的结构.
- 在没有和存在TFIIS的情况下对EC的分析.
- 结构性比较以确定替代的NELF结合模式及其与DNA和核酶体的相互作用.
主要成果:
- 冷电磁结构揭示了由于没有TFIIS的NELF-核细胞冲突而被追溯/逮捕的EC.
- 确定了两个不同的NELF结合模式,包括NELF-E与下游DNA的关键相互作用.
- 结合TFIIS促进了EC向核酶体的进展,形成了一个与部分未包裹的核酶体组成的暂停复合体,阻止了进一步的延长.
结论:
- 这项研究揭示了RNAPII在+1核酶体中暂停的结构基础,突出了NELF,TFIIS和核酶体之间的相互作用.
- NELF - 核酶体冲突导致最初的停滞,而TFIIS 则将EC 绑定重新定位以建立稳定的暂停状态.
- 这些发现提供了一种机理性的理解转录调节在促进器-核酶体边界.
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