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関連する概念動画

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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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Master Transcription Regulators02:23

Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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Cell Specific Gene Expression01:58

Cell Specific Gene Expression

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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
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アディポス由来の循環するmiRNAは,他の組織における遺伝子発現を調節する

Thomas Thomou1, Marcelo A Mori2, Jonathan M Dreyfuss3,4

  • 1Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.

Nature
|February 16, 2017
PubMed
まとめ

脂肪組織は,代謝を調節する外体RNA (miRNA) を放出する. ネズミの脂肪組織を回復させることで,グルコース耐性が向上し,FGF21が減少し,外体ミRNAが新しいアディポキンとして作用することを示唆した.

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Tissue-specific miRNA Expression Profiling in Mouse Heart Sections Using In Situ Hybridization
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Author Spotlight: Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator
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Tissue-specific miRNA Expression Profiling in Mouse Heart Sections Using In Situ Hybridization
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科学分野:

  • 代謝の調節
  • 分子生物学
  • 内分泌学

背景:

  • アディポース組織は,アディポキンを介してエネルギーホメオスタシスと代謝制御に中心的です.
  • エクソソームのマイクロRNA (miRNA) は細胞間通信に関与する.
  • 脂肪組織の調節不良は代謝障害と関連している.

研究 の 目的:

  • 代謝調節における脂肪組織に由来する外体ミRNAの役割を調査する.
  • 脂肪組織からの外体ミRNAがシグナル分子の役割を果たすかどうかを判断する.
  • 脂肪組織から派生したエクソソムの 治療の可能性を探るため

主な方法:

  • 脂肪組織特異的なDicerノックアウト (ADicerKO) を生成したマウス.
  • リポディストロフィーの患者のデータをヒト関連として利用した.
  • 脂肪組織移植の実験を行いました
  • 投与された正常およびADicerKO血清エクソソーム.
  • 評価されたグルコース耐性および肝臓Fgf21発現.
  • in vivo の miRNA 移転モデルを使用した.

主要な成果:

  • ADicerKOマウスとリポジストロフィー患者では,循環中の外体ミRNAが減少した.
  • 脂肪組織移植により,循環中のmiRNAレベルが回復し,ADicerKOマウスのグルコース耐性が改善されました.
  • 肝臓のFgf21mRNAと循環中のFGF21も減少した.
  • 正常な血清エクソソームは,ADicerKOエクソームではないが,これらの遺伝子調節効果を模倣した.
  • 遠隔組織間の miRNA 移転はエクソソマの活動を示した.

結論:

  • 脂肪組織は,循環する外体ミRNAの重要な源である.
  • 遠隔臓器における遺伝子発現を制御する信号分子として機能する.
  • エクソソームのmiRNAは,代謝疾患に対する潜在的な治療効果を持つアディポキンの新種である.