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相关概念视频

RNA Interference01:23

RNA Interference

24.4K
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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Experimental RNAi02:15

Experimental RNAi

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RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
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siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

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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.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
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Small interfering RNAs (siRNA)02:30

Small interfering RNAs (siRNA)

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Translational Regulation01:29

Translational Regulation

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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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Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
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相关实验视频

Updated: May 6, 2026

MISSION esiRNA for RNAi Screening in Mammalian Cells
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MISSION esiRNA for RNAi Screening in Mammalian Cells

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从计算选中获得的短干扰RNA导向链修饰剂.

Kazumitsu Onizuka1, Jason G Harrison, Alexi A Ball-Jones

  • 1Department of Chemistry, University of California, Davis , One Shields Ave, Davis, California 95616, United States.

Journal of the American Chemical Society
|October 25, 2013
PubMed
概括
此摘要是机器生成的。

对短干扰RNA (siRNA) 的化学修改增强了它们的药物潜力. 研究人员发现了siRNA导向链的新功能修改,提高了基因沉默效率.

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相关实验视频

Last Updated: May 6, 2026

MISSION esiRNA for RNAi Screening in Mammalian Cells
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MISSION esiRNA for RNAi Screening in Mammalian Cells

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A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
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Using In Vitro and In-cell SHAPE to Investigate Small Molecule Induced Pre-mRNA Structural Changes
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Using In Vitro and In-cell SHAPE to Investigate Small Molecule Induced Pre-mRNA Structural Changes

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科学领域:

  • 生物化学 生物化学
  • 分子生物学分子生物学
  • 药物发现 药物发现 药物发现

背景情况:

  • 短干扰RNAs (siRNAs) 是针对各种疾病的强有力的治疗剂.
  • 原生RNA结构对siRNA药物开发有局限性,需要进行化学修改.
  • 人类Argonaute 2 (hAgo2) 蛋白质是RNA干扰 (RNAi) 途径有效性的核心.

研究的目的:

  • 为了发现siRNA导向链的5个末端的功能化学修饰.
  • 利用hago2的计算选和结构数据来指导修改发现.
  • 为增强的siRNA疗法扩大核酸类比的范围.

主要方法:

  • 对潜在的siRNA修改进行结构引导的计算选.
  • 利用人类Ago2 (hAgo2) 的高分辨率结构.
  • 在RNA中合成和测试1,2,3-三-4-基和 purin衍生物.

主要成果:

  • siRNA导向链的5eal-end核酸需要在 hAgo2结合点中适当的形状互补性,不一定是沃森-克里克H结合.
  • 通过CuAAC反应合成的1,2,3-Triazol-4-yl基是siRNA 5终端的有效修饰.
  • 经过修改的Hoogsteen面或N2替代物的纯原衍生物被发现不适合5eal-end修改.
  • 一种缺乏沃森-克里克H结合能力的1,2,3-三-4-基在导向链的位置12显示出有效性.

结论:

  • 功能性siRNA修改可以通过结构引导的计算方法来发现.
  • 新型核酸类似物,如1,2,3-triazol-4-yl基,为siRNA药物设计提供了新的可能性.
  • 了解hago2-siRNA相互作用是开发更有效siRNA治疗方法的关键.