RNAポリメラーゼII転写前始動複合体の構造
Kenji Murakami1, Hans Elmlund, Nir Kalisman
1Department of Structural Biology, Stanford University, Stanford, CA 94305, USA.
まとめ
研究者らはRNAポリメラーゼIIの転写前始動複合体 (PIC) をマッピングした. 構造は,DNAのエントリーのためにRNAポリメラーゼIIの上に置かれている転写因子と相互作用するプロモーターDNAを明らかにします.
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
- バイオケミストリー バイオケミストリー
背景:
- RNAポリメラーゼII (pol II) は,遺伝子転写に中心的な役割を果たしています.
- 前始動複合体 (PIC) は,転写が始まる前に遺伝子プロモーターに組み込まれます.
- PICの構造を理解することは,転写規制の解読に不可欠です.
研究 の 目的:
- 完全な32タンパク質RNAポリメラーゼIIトランスクリプション前始動複合体 (PIC) の高解像度構造を決定する.
- PIC内の一般的な転写因子 (GTF) とpol IIの空間的配置を解明する.
- PICがトランスクリプションの開始にどのように準備されているかを理解する.
主な方法:
- PICを視覚化するために,冷凍電子顕微鏡 (cryo-EM) が使用されました.
- 質量スペクトロメトリー (XL-MS) と組み合わせた化学クロスリンクは,サブユニット相互作用をマッピングするために使用されました.
- 統合的構造分析は,これらのデータセットを組み合わせた.
主要な成果:
- 32タンパク質のPICは,GTFsとpol IIを分離する明確な二者組織を示した.
- プロモーターDNAは,ポリII活性部位裂け目の上に位置するGTFのみと関連していることが判明しました.
- DNAは,開始前の状態では,Pol IIと直接接触しなかった.
結論:
- 決定されたPIC構造は,転写開始のための平衡状態を明らかにします.
- 構造的な配置は,アクティブな転写バブルへの移行を容易にする.
- これは,トランスクリプションの重要なステップである pol II 裂け目にDNAが入り込むための位置づけです.
関連する概念動画
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...
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
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...


