RNAポリメラーゼIIの転写と結合したRNA干渉誘導クロマチンの改変
Vera Schramke1, Daniel M Sheedy, Ahmet M Denli
1Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, King's Buildings, University of Edinburgh, Edinburgh EH9 3JR, UK.
Nature
|June 21, 2005
まとめ
分裂酵母におけるRNA干渉 (RNAi) は,クロマチンを改変するために同類のDNA配列の転写を必要とします. このプロセスはRNAポリメラーゼIIの活動と結合し,転写を強調します.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- エピジェネティクス エピジェネティクス
背景:
- RNA干渉 (RNAi) は,遺伝子発現を調節するために小さな干渉RNA (siRNAs) を使用する保存された生物学的プロセスです.
- ユカリオットでは,siRNAsは,メッセンジャーRNAの分解や,同類のゲノムロシオのエピジェネティック改変につながる可能性があります.
- siRNAがDNAまたはクロマチンの改変を誘発する正確なメカニズムは,完全に理解されていません.
研究 の 目的:
- 分裂酵母 (Schizosaccharomyces pombe) のRNAi誘導クロマチンの改変における転写の役割を調査する.
- 異体転写がRNAi媒介の表遺伝的変化を誘発するのに十分であるかどうかを判断する.
- このプロセスにおけるRNAポリメラーゼIIとその調節ドメインの関与を解明する.
主な方法:
- 分裂酵母 (Schizosaccharomyces pombe) をモデル生物として利用しています.
- RNAi誘導クロマチンの改変における同質DNA配列転写の必要性を調査する.
- RNAi媒介サイレンシングに対する外部転写 (T7ポリメラーゼ) の影響を評価する.
- 重要なRNAiエフェクタータンパク質であるAgo1の標的トランスクリプトとRNAポリメラーゼIIとの関連を調べた.
- RNAポリメラーゼIIのカルボキシ末端領域 (CTD) の断片が転写サイレンシングに与える影響を分析した.
主要な成果:
- 分裂酵母におけるRNAiによって導かれたクロマチンの改変は,同類のDNA配列が転写された場合にのみ発生する.
- T7ポリメラーゼによる外部転写は,これらのクロマチンの改変を誘導するのに不十分です.
- Ago1は,ターゲットトランスクリプトとRNAポリメラーゼIIの両方と結合する.
- RNAポリメラーゼIICTDの破壊は,RNAi誘導による転写サイレンシングを損なう.
結論:
- 転写活動は,分裂酵母におけるRNAi媒介のクロマチンの改変に不可欠である.
- RNAi誘導による表遺伝的変化は,内生的な転写機構と結合し,特にRNAポリメラーゼIIが関与する.
- この発見は,RNAポリメラーゼIIによる新生トランスクリプトのsiRNA誘導ターゲティングがクロマチン変異とトランスクリプションサイレンシングにつながるメカニズムを示唆しています.
関連する概念動画
01:23Types of RNA
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
02:36RNA 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...
02:41Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
01:47Transcription 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...
01:20Types of RNA
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
RNA Performs Diverse...
02:36RNA 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...