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MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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MicroRNAs01:22

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RNA Interference01:23

RNA Interference

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RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
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siRNA - Small Interfering RNAs02:30

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Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
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Nucleic Acid Structure01:25

Nucleic Acid Structure

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The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
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Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells
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Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells

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マイクロRNAターゲティングの構造的基礎

Nicole T Schirle1, Jessica Sheu-Gruttadauria1, Ian J MacRae2

  • 1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Science (New York, N.Y.)
|November 1, 2014
PubMed
まとめ
この要約は機械生成です。

この研究は,アルゴナウト-2 (Ago2) タンパク質がマイクロRNA (miRNA) とターゲットメッセンジャーRNA (mRNA) とどのように相互作用するかを明らかにしています. 構造的な洞察は,保存された標的認識機構と,Ago2が望ましくない遺伝子サイレンシングをどのように防ぐかを説明します.

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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
  • 遺伝学 遺伝学とは

背景:

  • マイクロRNA (miRNA) は,真核生物における遺伝子発現の重要な調節因子である.
  • アルゴナウトタンパク質,特にアルゴナウト-2 (Ago2) は,miRNAの機能の中心です.
  • Ago2-miRNA-mRNAの相互作用メカニズムを理解することは,遺伝子調節を解読する上で極めて重要です.

研究 の 目的:

  • 人間のアルゴナウト-2 (Ago2) がガイドRNAや標的RNAと相互作用する構造的基礎を解明する.
  • Ago2による標的認識の段階的なメカニズムを明らかにする.
  • シーケンスインデペンデントとシーケンス固有の認識機能を説明します.

主な方法:

  • X線結晶学を用いて,人間のAgo2の構造を決定した2.
  • Ago2の構造は,単独でガイドRNAに結合し,標的RNAとの複合体として得られた.
  • タンパク質と核酸の相互作用と形状の変化の分析.

主要な成果:

  • Ago2は,最初のターゲットペアリングのために,特定のガイドRNAヌクレオチド (nt2-5) を暴露します.
  • ターゲットの結合は,形状の変化を誘導し,認識のためにより多くのガイドRNA領域を暴露します.
  • Ago2は,マイナー・グリューブ・インタラクションとアデノシン・バインディング・ポケットをターゲット・インタビュレーションに活用しています.
  • マグネシウムイオンの調整メカニズムは,偽の標的RNAの分裂を防ぐ.

結論:

  • この研究は,miRNA媒介による遺伝子サイレンシングの詳細な構造的メカニズムを提供します.
  • 保存された動物のmiRNA標的部位認識パターンは,観察された相互作用によって説明されています.
  • Ago2の構造は,初期および広範なターゲット認識の両方を容易にし,同時に特異性を確保し,オフターゲット効果を防止します.