从成千上万的随机引子中学到的内部介导增强的序列依赖和独立效应
Emma J K Kowal1, Yuta Sakai1, Michael P McGurk1
1Department of Biology, Massachusetts Institute of Technology, Cambridge MA 02139, United States.
Nucleic acids research
|February 25, 2025
概括
大多数合成内子有效地增强基因表达,这一过程称为内子介导增强 (IME). 这种基因表达增强在很大程度上独立于特定的内子序列,突出了拼接拼接.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 基因规则 基因规则
背景情况:
- 结合体内基因在真核基因中很常见,可以增强基因表达 (内基因介导增强,IME).
- 内子序列在调节IME大小中的确切作用仍然在很大程度上未被描述.
- 了解IME对于理解真核生物中的基因表达调节至关重要.
研究的目的:
- 为了研究不同内子序列对基因表达的影响.
- 为了确定内部序列是否显著影响内部介导增强的幅度.
- 确定导致IME的依赖于序列的因素.
主要方法:
- 在人类细胞中使用了大规模并行报告者测试 (MPRA).
- 测试了数以万计的合成内子与自然拼接部位和随机内部序列.
- 在mRNA和蛋白质水平上量化基因表达.
主要成果:
- 大多数合成内子都表现出高效的拼接和增强的基因表达,与自然内子相当或超过.
- 几乎所有测试的内子都增加了基因表达的约八倍,与无内子对照相比.
- IME强度与拼接效率和内部聚尿素延伸的存在正相关.
结论:
- 内部介导增强是拼接的一般性质,在很大程度上独立于特定的内部序列.
- 虽然存在依赖序列的方面,但IME的主要机制似乎是拼接过程本身.
- 这项研究提供了对内部介导基因表达增强的序列独立性质的见解.
相关概念视频
Chromatin Structure Regulates pre-mRNA Processing
6.9K
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...
6.9K
Alternative RNA Splicing
20.9K
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...
20.9K
RNA Splicing
55.9K
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...
55.9K
Exon Recombination
3.5K
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...
3.5K
Regulation of Expression Occurs at Multiple Steps
22.4K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.4K
Regulation of Expression at Multiple Steps
864
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
864


