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関連する概念動画

Eukaryotic RNA Polymerases00:58

Eukaryotic RNA Polymerases

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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...
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Eukaryotic RNA Polymerases00:58

Eukaryotic RNA Polymerases

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The Replisome03:01

The Replisome

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DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
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The Replisome03:01

The Replisome

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Transcription Initiation01:47

Transcription Initiation

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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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Bacterial RNA Polymerase00:43

Bacterial RNA Polymerase

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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...
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関連する実験動画

Updated: Dec 18, 2025

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
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SARS-CoV-2ポリメラーゼによるRNA複製の構造的基礎

Quan Wang1, Jiqin Wu2, Haofeng Wang3

  • 1Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

Cell
|June 12, 2020
PubMed
まとめ

SARS-CoV-2のRNA複製を理解することは,COVID-19治療の鍵です. この研究は,ウイルスのポリメラーゼ複合体の構造とレムデシビルがそれを阻害する方法を明らかにし,コロナウイルスの複製機構の洞察を提供します.

キーワード:
2019-nCoV についてコロナウイルスRdRP についてSARS-CoV-2についてファビピラビールnsp12 についてnsp8 についてポリメラーゼレムデシビルウイルス

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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

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Last Updated: Dec 18, 2025

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
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Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

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科学分野:

  • 構造生物学
  • ウイルス学
  • 生物化学

背景:

  • レムデシビルのようなヌクレオチドアナログ阻害剤は,COVID-19治療において有望であることが示されています.
  • SARS-CoV-2のRNA依存RNAポリメラーゼ (nsp12) との正確な薬物相互作用は,まだ完全に理解されていません.

研究 の 目的:

  • SARS-CoV-2 RNA複製の分子メカニズムを解明する.
  • レムデシビルによる抑制の構造的根拠を調査する.

主な方法:

  • 停滞したSARS-CoV-2ポリメラーゼ複合体の冷凍電子顕微鏡 (冷凍EM) 構造 (転移前および転移後) を決定した.
  • レムデシビルのトリフォスファート代謝物の構造と運動分析を行った.
  • プリマースからポリマース複合体への移行モデルを提案した.

主要な成果:

  • 核酸結合時に,nsp12とその共因子 (nsp7,nsp8) の重要な構造的再配置が観察されました.
  • 核酸の組み込みに不可欠なnsp12の保存された残留物を特定した.
  • レムデシビールの抑制メカニズムを特徴づけた.

結論:

  • SARS-CoV-2ポリメラーゼ複合体の構造的な洞察は,ウイルスのRNA複製を理解するための基礎を提供します.
  • この発見は,効果的なコロナウイルス転写および複製阻害剤の開発のヒントを提供します.