RNA聚合酶II逆行,停止和重新激活的结构基础
Alan C M Cheung1, Patrick Cramer
1Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
Nature
|February 25, 2011
概括
RNA聚合酶II (Pol II) 的逆向跟踪阻止了转录. 转录因子IIS (TFIIS) 通过诱导RNA分裂来重新激活Pol II,这是细胞存活和基因调节的关键过程.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 基因法规 基因法规
背景情况:
- RNA聚合酶II (Pol II) 将DNA转录为mRNA,但可以因回溯而停止.
- 聚二阻断转录,需要通过转录因子IIS (TFIIS) 来重新激活细胞活力.
- 这些过程对于导航核体和调节促进体附近的基因表达至关重要.
研究的目的:
- 阐明Pol II背后的结构机制,包括追溯,逮捕和TFIIS中介的重新激活.
- 为理解转录延长控制提供一个结构框架.
主要方法:
- 采用X射线晶体学来确定被捕的Pol II复合物的结构.
- 结构以3.3 Å分辨率得到分辨,包括一个被阻止的Saccharomyces cerevisiae Pol II复合体与DNA和RNA.
- 一个含有Pol II,DNA,RNA和TFIIS的反应中间体复合体也在结构上进行了表征.
主要成果:
- 被捕获的复合体揭示了逆向RNA占据了"逆向位置",捕获触发环并抑制延长.
- 在与TFIIS结合的中间体中,TFIIS重新定位触发循环,取代RNA,并可能促进RNA裂变.
- 鉴定出了一种"打开氨酸"残留物,可能会限制RNA回溯的程度.
结论:
- 该研究建立了Pol II回溯,逮捕和TFIIS依赖的重新激活的详细结构基础.
- 这些发现提供了关于转录延长如何在特定的DNA序列和基因表达过程中受到调节的见解.
- 结构框架有助于进一步分析转录动态及其在细胞过程中的作用.
相关概念视频
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...
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...
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...
Restarting Stalled Replication Forks
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...


