RNAポリメラーゼIIの転写忠節性を支配する化学相互作用を剖析する
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
まとめ
RNAポリメラーゼII (Pol II) の転写信頼性の維持は極めて重要です. この研究は,水素結合が核酸の組み込みの鍵であるが,拡張ではないことを明らかにし,ベーススタッキングと振動ペアは精度を保証する.
科学分野:
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
- 遺伝学 遺伝学とは
背景:
- RNAポリメラーゼII (Pol II) は,真核生物におけるメッセンジャーRNAを合成する.
- 核酸選択,組み込み,拡張,校正のチェックポイントを持つトランスクリプションの忠誠性は不可欠です.
- DNAの損傷は,転写の信頼性を損なう可能性がありますが,その背後にある化学的メカニズムは完全に理解されていません.
研究 の 目的:
- Pol IIの転写精度チェックポイントを制御する化学相互作用を分析する.
- 微妙なDNA損傷がトランスクリプションの忠誠度をどのように低下させるかの分子基礎を解明する.
- Pol IIの精度に対する静電効果とステリック効果を体系的に評価する.
主な方法:
- Pol IIの相互作用を調査するために"水素結合欠乏"の核酸類を用いました.
- 分析された нуклеотиドの選択,組み込み,トランスクリプトの拡張,および校正のステップ.
- 水素結合,塩基堆積,および塩基サイズ差別の役割を調査した.
主要な成果:
- 水素結合は,ヌクレオチドの組み込みには重要ですが,マッチしたRNA端からの拡張には重要ではありません.
- トランスクリプト拡張の信頼性は,U:T振動ペアのような不正な水素結合パターンを区別することに強く依存しています.
- 水素結合とベーススタッキングの両方がPol II校正に影響を与えます; 強いベーススタッキングは,失われた水素結合を補うことができます.
- Pol IIは,テンプレートベースの微妙なサイズ違いを検出することができます.
結論:
- 水素結合,塩基の積み重ね,および塩基の大きさは,Pol IIの転写精度の決定的な決定因子である.
- 振動基の相互作用は,不一致の拡張を防ぐために不可欠です.
- この研究は,Pol IIの精度制御における静電およびステリック要因の体系的な評価を提供します.
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...
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...


