替代拼接按阶段对器官发育进行分类,并揭示与神经肌肉疾病相关的独特人类拼接变体
Chen Li1, Fu-Xing Gong1, Zhigang Yang1
1Research Center of Plastic Surgery Hospital, CAMS Key Laboratory of Tissue and Organ Regeneration, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
The Journal of biological chemistry
|April 27, 2025
概括
替代拼接 (AS) 产生了对器官发育至关重要的蛋白质多样性. 这项研究揭示了人类和老鼠大脑/心脏发育中的特定物种的AS模式,将改变的拼接与神经发育障碍联系起来.
科学领域:
- 基因组学和发育生物学
- 分子生物学和遗传学分子生物学和遗传学
背景情况:
- 替代拼接 (AS) 产生蛋白质多样性,有助于器官发育的物种特异性差异.
- 了解特定阶段的拼接变体对于破译发育过程和疾病相关性至关重要.
研究的目的:
- 在人类和小鼠大脑和心脏发育过程中调查特定阶段的替代拼接变体.
- 确定替代拼接事件与疾病,特别是神经发育障碍之间的相关性.
- 探索替代拼接中的特定物种差异及其功能影响.
主要方法:
- 时间转录组分析以描述基因表达和拼接模式.
- 拼接因子 (SF) 和发育动态替代拼接基因 (devASG) 的识别和分类.
- 对人类和小鼠发育阶段之间的拼接变异和疾病丰富的比较分析.
主要成果:
- 拼接因子准确地分类器官发育阶段,5 SFs在人类器官生成中被上调.
- 在类似的人类和小鼠发育阶段观察到的跨阶段拼接变化.
- 在神经发育障碍方面, devASG 富含神经发育障碍,人类新生儿大脑和胎儿心脏发生显著变化;与曼诺斯糖化和纤毛细胞运动相关的人类特异性神经肌肉 devASG.
结论:
- 拼接因素和替代拼接事件是有机体发生的重要驱动因素.
- 发育动态的替代拼接基因与神经发育障碍有关.
- 特定物种的AS模式,特别是神经肌肉功能,为人类特定疾病提供了洞察力,并为翻译研究模型提供了信息.
相关概念视频
01:32RNA Splicing
56.2K
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...
56.2K
02:18Alternative RNA Splicing
21.1K
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...
21.1K
01:36Pre-mRNA Processing: RNA Splicing
5.2K
5.2K
02:32Exon Recombination
3.6K
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...
Exon shuffling follows “splice frame rules.” Each exon...
3.6K
02:41Chromatin Structure Regulates pre-mRNA Processing
7.0K
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...
7.0K
02:41Chromatin Structure and RNA Splicing
2.7K
2.7K