解开人类基因组中罕见的内类的空间组织和拼接
Saren M Springer1, Katherine Fleck2,3, Kaitlin N Girardini1
1Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA.
bioRxiv : the preprint server for biology
|August 20, 2025
概括
内部子类表现出明显的三维 (3D) 基因组组织. 聚合效率,特别是对于较小的内子,是由内子的身份决定的,而不仅仅是它们的核定位.
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 三维 (3D) 基因组组织影响基因调节,包括转录和RNA处理.
- 基因的空间定位在前传递 RNA (前mRNA) 拼接中的作用是一个新兴的研究领域.
- 了解不同类型的3D组织及其对拼接的影响至关重要.
研究的目的:
- 在四个人类细胞系中绘制六个内部类的空间组织.
- 调查3D基因组中的内部组织是否影响它们的拼接效率.
- 确定内部子类,核定位和拼接结果之间的关系.
主要方法:
- 使用Hi-C,TSA-seq和DamID-seq来绘制内核的3D基因组组织.
- 分析了六个内部类:主要类,次要类,次要类,混合类和非正规类.
- 综合空间组织数据与RNA测序 (RNA-seq) 数据以评估拼接效率.
主要成果:
- 在活性区 (A) 和斑点相关域 (SPADs) 中,小内子被丰富,而在膜相关域 (LADs) 中则被耗尽.
- 混合和非正规的内核与小内核相比显示了基因组组织的反向趋势.
- 拼接效率主要取决于内子身份,而不是核位置,在癌细胞中观察到的一些例外.
- 在SPAD以外的癌细胞中,小内核拼接效率高于纤维细胞,这表明3D定位之外的因素.
结论:
- 内部子类显示不同的三维基因组组织模式.
- 内子身份,而不是空间定位,是小内子拼接效率的主要决定因素.
- 观察到的剪接效率模式在细胞类型之间有所不同,这表明细胞类型特定的调节机制.
相关概念视频
02:07Organization of Genes
69.3K
Overview
69.3K
01:32RNA Splicing
56.9K
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...
56.9K
02:18Alternative RNA Splicing
21.7K
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...
21.7K
02:32Exon Recombination
3.7K
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...
3.7K
02:41Chromatin Structure and RNA Splicing
2.8K
2.8K
02:41Chromatin Structure Regulates pre-mRNA Processing
7.2K
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...
7.2K