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相关概念视频

RNA Splicing01:32

RNA Splicing

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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.4K
Alternative RNA Splicing02:18

Alternative RNA Splicing

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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
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Exon Recombination02:32

Exon Recombination

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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon...
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Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
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Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells
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异常拼接在ALS/FTD中使C9ORF72重复扩张变异.

Suzhou Yang1,2, Denethi Wijegunawardana1,2, Udit Sheth3,4

  • 1Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.

bioRxiv : the preprint server for biology
|November 28, 2023
PubMed
概括

C9ORF72基因的核酸重复扩张 (NRE) 导致ALS和FTD. 这项研究揭示了NRE触发异常拼接,影响RNA输出和翻译,为这些神经退行性疾病提供了新的见解.

关键词:
在ALS/FTD中,C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C9ORF72C隐秘的拼接地点.在mRNA拼接过程中.核酸重复扩张扩张

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科学领域:

  • 遗传学 是一个遗传学.
  • 神经科学是一个神经科学.
  • 分子生物学分子生物学

背景情况:

  • C9ORF72基因核酸重复扩张 (NRE) 是肌缩侧面硬化症 (ALS) 和前性痴呆症 (FTD) 的主要遗传原因.
  • 内部NREs影响细胞质翻译机制的机制尚不清楚.

研究的目的:

  • 调查C9ORF72基因中的内基NREs是如何从核中处理和出口的.
  • 确定异常拼接在C9ORF72相关的ALS和FTD病变发生过程中的作用.

主要方法:

  • 从患者衍生细胞中捕获和测序含有NRE的RNA.
  • 在患者衍生的运动神经元和人类大脑组织中分析C9ORF72异常拼接.
  • 报告员测试评估NRE对密码拼接部位激活的影响.

主要成果:

  • 发现C9 NRE通过下游5拼接位的使用而被外化,导致它们从核中以各种拼接的mRNA异型形式出口.
  • 在NRE阳性运动神经元和脑组织中,C9ORF72的异常拼接显著增加.
  • 病理性的NREs足以激活记者mRNA中的神秘拼接位.

结论:

  • 重复诱导的异常拼接在NRE含有RNAs的生物发生,核出口和翻译中发挥着关键作用.
  • 异常拼接是将C9ORF72 NREs与ALS和FTD病原体联系起来的关键机制.