一个依赖于IDR的机制,用于控制核受体与RNA聚合酶II的介质相互作用
Haiyan Zhao1, Jiaqin Li1, Yufei Xiang2
1Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA.
Molecular cell
|July 2, 2024
概括
核受体通过调节中间体复合体来控制转录启动.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 生物化学 生物化学
背景情况:
- 中介体 (MED) 复合体对于真核生物的基底转录至关重要.
- 它在特定子单元的激活剂依赖转录和调节中的作用尚不清楚.
研究的目的:
- 研究MED26亚单元和CDK8激酶模块 (CKM) 如何调节与RNA聚合酶II (RNA Pol II) 的中间体复合相互作用.
- 阐明核受体 (NR) 影响这种相互作用的机制.
主要方法:
- 对CKM-MED相互作用的生物化学分析.
- 低温电子显微镜 (cryo-EM) 和交联质谱法 (XL-MS).
主要成果:
- 该CKM抑制了与MED结合的RNA Pol II碳酸终端域 (CTD).
- 与CKM-MED结合的核受体以MED26依赖的方式缓解了这种抑制.
- 结构分析显示,MED13中的一个内在无序区域 (IDR) 在NR结合时重新定位,使CTD相互作用成为可能.
结论:
- 核受体为CKM-MED复合体进行MED26依赖的RNA Pol II相互作用,从而控制转录启动.
- 这为调节基因表达提供了核受体和中介体复合体之间的机械联系.
相关概念视频
RNA Polymerase II Accessory Proteins
9.2K
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...
9.2K
Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
Co-activators and Co-repressors
7.3K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.3K
Chromatin Structure Regulates pre-mRNA Processing
7.0K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.0K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Transcription Initiation
16.4K
Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
The promoters and enhancers and their accessory proteins allow tight regulation of...
16.4K


