在 hnRNP C 和 U2AF65 之间的直接竞争保护了转录组免受 Alu 元素的外电化
Kathi Zarnack1, Julian König, Mojca Tajnik
1European Molecular Biology Laboratory (EMBL) European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Cell
|February 5, 2013
概括
人类基因组含有众多的Alu元素,这些元素可以破坏基因功能. RNA结合蛋白 hnRNP C 防止这些元素被错误地纳入信使RNA,保护转录组的完整性.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 在RNA分离过程中.
背景情况:
- 人类基因组在转录区域内包含大约65万个Alu元素.
- 元素具有神秘的拼接部位,构成异常纳入成熟转录的风险,并威胁到转录组完整性.
- 阻止Alu元素外化的分子机制在很大程度上仍然未知.
研究的目的:
- 阐明人体转录组被保护免受可转换元素异常外电化的机制.
- 调查RNA结合蛋白 hnRNP C 在防止 Alu 元素被纳入中的作用.
主要方法:
- 量化ICLIP (个人核酸分辨率交联免疫沉) 来绘制RNA结合蛋白相互作用的地图.
- 迷你基因测试用于研究拼接事件和突变的影响.
- 在真实和隐性拼接部位对hNRNP C和U2AF65结合的分析.
主要成果:
- hnRNP C在许多拼接点上与拼接因子U2AF65竞争,包括Alu元素中的拼接点.
- 丧失hNRNP C功能的结果是先前被抑制的Alu外显子的形成,导致转录功能的显著破坏.
- 发现Alu元素中的与疾病相关的突变会损害hNRNP的C结合,从而解释了它们的有害影响.
结论:
- hnRNP C通过阻止U2AF65与Alu元素结合,从而保护转录组完整性,充当全基因组的哨兵.
- 这种机制对于保护人类转录组免受可转移元素的破坏性影响至关重要.
- 这些发现对理解人类进化和与Alu元素相关的疾病的遗传基础有重大影响.
相关概念视频
RNA Splicing
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...
Alternative RNA Splicing
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...
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...
Alternative RNA Splicing
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...
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...
Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
Exon Recombination
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 has three reading...
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Nonsense-mediated mRNA Decay
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,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...


