一个RNA聚合酶II转录前启动复合物的架构
Kenji Murakami1, Hans Elmlund, Nir Kalisman
1Department of Structural Biology, Stanford University, Stanford, CA 94305, USA.
概括
研究人员绘制了RNA聚合酶II转录前启动复合体 (PIC) 的地图. 该结构揭示了促进者DNA与转录因子相互作用,位于RNA聚合酶II上方,用于DNA输入.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- RNA聚合酶II (pol II) 是基因转录的核心.
- 在转录开始之前,预启动复合体 (PIC) 聚集在基因促进体上.
- 了解PIC结构对于破译转录调节至关重要.
研究的目的:
- 确定完整的32蛋白RNA聚合酶II转录前启动复合体 (PIC) 的高分辨率结构.
- 阐明PIC内部的一般转录因子 (GTF) 和pol II的空间布局.
- 了解PIC如何准备进行转录启动.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 可视化了PIC.
- 化学交叉链接与质谱学 (XL-MS) 相结合,用于绘制子单位相互作用的地图.
- 综合性结构分析将这些数据集结合起来.
主要成果:
- 32种蛋白质的PIC表现出一种独特的两方组织,将GTF和pol II分开.
- 发起者DNA被发现仅与GTFs相关,位于pol II活性位点裂上方.
- 在启动前的状态下,DNA并没有直接接触到pol II.
结论:
- 确定的PIC结构显示了转录启动的平衡状态.
- 结构布局促进过渡到一个活跃的转录泡.
- 这将DNA置于进入pol II裂的位置,这是转录的关键步骤.
相关概念视频
Transcription Initiation
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The promoters and enhancers and their accessory proteins allow tight regulation of...
The promoters and enhancers and their accessory proteins allow tight regulation of...
General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
Eukaryotic RNA Polymerases
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All three eukaryotic RNAPs require specific transcription factors, of which the...
All three eukaryotic RNAPs require specific transcription factors, of which the...
Eukaryotic RNA Polymerases
RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
All three eukaryotic RNAPs require specific transcription factors, of which the...


