RNAポリメラーゼIIの逆行,停止,再活性化の構造的基礎
Alan C M Cheung1, Patrick Cramer
1Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany.
Nature
|February 25, 2011
まとめ
RNAポリメラーゼII (Pol II) のバックトラッキングは,転写を停止する. 転写因子IIS (TFIIS) は,細胞生存と遺伝子調節のための重要なプロセスであるRNA分裂を誘導することによってPol IIを活性化します.
科学分野:
- 分子生物学は分子生物学である.
- 構造生物学 構造生物学とは
- 遺伝子規制 遺伝子規制
背景:
- RNAポリメラーゼII (Pol II) はDNAをmRNAに転写しますが,バックトラッキングにより停止することができます.
- Pol II arrestは転写を停止し,細胞生存のために転写因子IIS (TFIIS) によって再活性化する必要があります.
- これらのプロセスは,核細胞をナビゲートし,プロモーターの近くの遺伝子発現を調節するために重要です.
研究 の 目的:
- Pol IIのバックトラッキング,逮捕,およびTFIIS媒介による再活性化の基礎となる構造的メカニズムを解明する.
- 転写延長制御を理解するための構造的枠組みを提供すること.
主な方法:
- 逮捕されたPol II複合体の構造を決定するために,X線結晶学が採用されました.
- 構造は3.3 Åの解像度で解像させられ,DNAとRNAを含むSaccharomyces cerevisiae Pol II複合体の解像度が停止しました.
- Pol II,DNA,RNA,TFIISを含む再活性化中間複合体も構造的に特徴づけられました.
主要な成果:
- 逮捕された複合体は,バックトラックされたRNAが"バックトラックサイト"を占有し,トリガーループを閉じ込め,延長を阻害することを明らかにした.
- TFIISに結合した中間体では,TFIISはトリガーループの位置を変更し,RNAを移動させ,RNAの分裂を容易にします.
- "ゲーティングチロシン"残留物が特定され,RNAのバックトラッキングの範囲を制限する可能性が高い.
結論:
- この研究は,Pol IIのバックトラッキング,逮捕,およびTFIISに依存する再活性化の詳細な構造的基礎を確立しています.
- これらの発見は,特定のDNA配列および遺伝子発現中に転写延長がどのように調節されるかについての洞察を提供します.
- 構造的枠組みは,転写ダイナミクスと細胞プロセスにおけるその役割のさらなる分析を容易にする.
関連する概念動画
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...
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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...
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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...
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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...
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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...


