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相关概念视频

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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Multi-species Conserved Sequences02:51

Multi-species Conserved Sequences

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Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale  studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
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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...
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Alternative RNA Splicing02:18

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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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Organization of Genes02:07

Organization of Genes

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Overview
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DNA-only Transposons02:57

DNA-only Transposons

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DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
The donor site from where the transposon is excised is either degraded or...
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人类的内子含有保存的特定组织的神秘毒素外子.

Sergey Margasyuk1, Antonina Kuznetsova1, Lev Zavileyskiy1

  • 1Center for Molecular and Cellular Biology, Skolkovo Institute of Science and Technology, Bolshoy Bulvar, 30, 121205, Moscow, Russia.

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概括

人类内子含有隐藏的神秘外子,可以表达,特别是在罕见的疾病或癌症中. 这些神秘的毒素外子在标准RNA测序中经常被遗漏,突出了当前基因注释中的差距.

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科学领域:

  • 基因组学就是基因组学.
  • 分子生物学分子生物学
  • 基因表达 基因表达

背景情况:

  • 替代拼接可以从单个基因生成大量的转录,但外基因目录是不完整的.
  • 人类内核含有未知功能的保存元素,可能包括调节或编码序列.
  • 在特定条件下表达的密码外基因可能有助于转录基因多样性.

研究的目的:

  • 为了调查人类蛋白质编码基因中保存的内基因元素是否代表了神秘的外基因.
  • 确定已识别的神秘外型的功能影响和表达模式.
  • 通过实验方法验证密码外子的表达.

主要方法:

  • 来自基因型-组织表达 (GTEx) 数据集的RNA-seq数据的分析,以确定潜在的神秘外型.
  • 隐秘的外型特征 (进化保护,阅读覆盖) 与注释的外型特征的比较.
  • 用循环赫西米德治疗的A549细胞的RNA测序以抑制无意中介衰变 (NMD).
  • 定量聚合酶连锁反应 (qPCR) 用于确认所选密码外基子的表达.

主要成果:

  • 在人类内核中发现了一组神秘的外,表现出与注释外相似的特征.
  • 许多已识别的密码外原体作为毒素外原体起作用,在纳入后导致NMD异型.
  • 有证据表明,这些神秘的前体的组织特异性和癌症特异性表达和调节.
  • 实验验证证证实了八个测试中的七个密码元的表达,特别是在NMD抑制后.

结论:

  • 人类蛋白质编码基因内子包含在保护区域内的神秘毒素外子.
  • 由于在标准RNA-seq库中代表性有限,这些神秘的外型通常没有注释.
  • 它们在特定条件下的表达和在NMD中的潜在作用凸显了它们在基因调节和疾病中的重要性.