剖析调控RNA聚合酶II转录忠实性的化学相互作用
Matthew W Kellinger1, Sébastien Ulrich, Jenny Chong
1Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, La Jolla, California 92093-0625, United States.
Journal of the American Chemical Society
|April 19, 2012
概括
保持RNA聚合酶II (Pol II) 的转录忠实性至关重要. 这项研究揭示了键是核酸结合的关键,但不是扩展,而基堆叠和摇摆对确保了准确性.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 遗传学 是一个遗传学.
背景情况:
- RNA聚合酶II (Pol II) 在真核生物中合成信使RNA.
- 转录忠实性至关重要,核酸选择,结合,扩展和校对都有检查点.
- DNA损伤可能会损害转录效率,但潜在的化学机制尚未完全理解.
研究的目的:
- 剖析控制Pol II转录保真性检查点的化学相互作用.
- 阐明微妙的DNA损伤如何降低转录保真性的分子基础.
- 系统地评估对Pol II保真度的静电和静电效应.
主要方法:
- 使用"缺乏键"的核酸相似物来探测Pol II相互作用.
- 分析了核酸选择,结合,转录扩展和校对步骤.
- 研究了结,堆叠和大小歧视的作用.
主要成果:
- 键对于核酸结合至关重要,但对于从匹配的RNA末端扩展至关重要.
- 转录扩展效率强烈依赖于区分不正确的键模式,如U:T摇摆对.
- 结合和基层堆叠都影响了Pol II校对;强大的基层堆叠可以弥补丢失的结合.
- 波尔II可以检测模板基的微妙尺寸差异.
结论:
- 结合,堆叠和大小是Pol II转录保真性的关键决定因素.
- 摆动基相互作用对于防止不匹配扩展至关重要.
- 这项工作提供了对Pol II保真性控制中的静电和静电因素的系统评估.
相关概念视频
Transcription Initiation
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...
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...
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...
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...
Bacterial RNA Polymerase
Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...


