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Translational Regulation01:29

Translational Regulation

862
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
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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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Regulation of Expression Occurs at Multiple Steps02:24

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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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Regulated mRNA Transport02:22

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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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FMRPは,タンパク質発現を調節するために異なるmRNA配列要素をターゲットにしています.

Manuel Ascano1, Neelanjan Mukherjee, Pradeep Bandaru

  • 1Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, The Rockefeller University, New York, New York 10065, USA.

Nature
|December 14, 2012
PubMed
まとめ
この要約は機械生成です。

脆いX症候群 (FXS) は,自閉症スペクトル障害 (ASD) と関連しています. 研究者らは,FMRPタンパク質のRNA標的を特定し,FXSとASDの新しい治療法の開発に不可欠な経路を明らかにしました.

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科学分野:

  • 遺伝学 遺伝学とは
  • 神経科学は神経科学である.
  • 分子生物学は分子生物学である.

背景:

  • 脆いX症候群 (Fragile X syndrome,FXS) は,知的障害を引き起こす遺伝疾患であり,自閉症スペクトル障害 (ASD) と関連しています.
  • FXSは,RNAの調節に不可欠なFMRPタンパク質を生成するFMR1遺伝子の発現が低下した結果である.

研究 の 目的:

  • RNA認識要素とFMRPおよびそのパラログ (FXR1P,FXR2P) の結合部位を特定する.
  • 標的mRNAへのFMRP結合が,さまざまな組織におけるタンパク質レベルとシグナル伝達経路にどのように影響するかを調査する.
  • FXSとASDの新たな治療目標の基礎を確立する.

主な方法:

  • FMRPにおけるRNA認識要素の特徴.
  • 野生型および変異型FMRPイソフォームおよびパラログのmRNA標的の特定.
  • 細胞培養,マウス卵巣,人間の脳組織における標的mRNAタンパク質レベルに対するFMRPの影響の分析.
  • Fmr1 (((-/-) マウスの卵巣における標的遺伝子不調の検査.

主要な成果:

  • FMRP,FXR1P,FXR2Pの異なるRNA認識要素と結合部位が特定されました.
  • FMRPの結合特性 (頻度,比率,分布) は,標的mRNAの関連性を決定する.
  • 多くのASDに関連した遺伝子がFMRP標的であることが判明し,FMRPはさまざまな生物学的文脈でタンパク質レベルに影響を与えます.
  • Fmr1 (((-/-) マウスの卵巣では,これらの標的の調節不全が観察され,共通のシグナル伝達経路を示唆しました.

結論:

  • FMRPのターゲットは,FXSとASDの両方に関連する保存されたシグナル伝達経路を共有しています.
  • この研究は,FXSやASDのような神経疾患の潜在的な治療標的のランク付けされたリストを提供します.
  • FMRP-RNAの相互作用を理解することは,FXSとASDの基礎にある分子メカニズムを解明する鍵です.