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相关概念视频

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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RNA Editing02:23

RNA Editing

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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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RNA Stability01:53

RNA Stability

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Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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Pre-mRNA Processing: Modification of pre-mRNA Ends01:35

Pre-mRNA Processing: Modification of pre-mRNA Ends

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In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
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mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
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N1-Methylpseudouridine和pseudouridine的修饰在翻译过程中调节mRNA解码.

Jeremy Monroe1, Daniel E Eyler1, Lili Mitchell2

  • 1Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.

Nature communications
|September 16, 2024
PubMed
概括

在信使RNA (mRNA) 中的N1-methylpseudouridine (m1Ψ) 修改不会显著改变蛋白质合成速度,但可以微妙地影响准确性. 修改后的编码子的环境会影响翻译效率,影响蛋白质的产生.

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科学领域:

  • 分子生物学分子生物学
  • 生物化学 生物化学
  • 遗传学 遗传学 是一个

背景情况:

  • 核糖体通过mRNA编码子和氨基酸-tRNA结合来确保蛋白质生产的准确性.
  • 化学修改mRNA核基可以改变结,影响蛋白质合成.
  • N1-methylpseudouridine (m1Ψ) 是治疗和疫苗mRNA的一个常见修改.

研究的目的:

  • 调查N1-甲基伪尤里丁 (m1Ψ) 修改对mRNA翻译速度和真实性的影响.
  • 要确定m1Ψ是否影响氨基酸结合的准确性和蛋白质合成的速度.

主要方法:

  • 在体外翻译试验测量氨基酸添加和终止率.
  • 在人体细胞中进行实验,以评估翻译的真实性.
  • 对mRNA:tRNA相互作用和能量学的计算建模.

主要成果:

  • m1Ψ修改并没有显著改变氨基酸添加或终止的速率常数.
  • m1Ψ微妙调制的氨基酸合并忠实度以一种依赖于编码子位置和tRNA的方式.
  • 计算建模表明改变的mRNA:tRNA相互作用能量解释了上下文依赖的错误编码.

结论:

  • m1Ψ 修改主要影响翻译准确度,而不是速度.
  • 经m1Ψ修饰的编码子的序列上下文决定了观察到的错误编码水平.
  • 了解这些影响对于优化基于mRNA的疗法和疫苗至关重要.