毒素外子:调RNA剪接用于针对性基因调控
Christopher R Neil1, Cassandra Schaening-Burgos1, Maria S Alexis1
1Remix Therapeutics, Watertown, MA, USA.
Trends in pharmacological sciences
|February 6, 2025
概括
毒素外子 (PE) 被拼接到mRNA中,通过无意中介衰变 (NMD) 准其降解. 这个过程调节了基因表达,并为疾病提供了新的治疗策略.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 在RNA生物学,RNA生物学.
背景情况:
- 无意中介衰变 (NMD) 是一个关键的mRNA质量控制途径.
- 最近的RNA测序进展揭示了NMD在通过拼接调节mRNA稳定性和丰富性的广泛作用.
- 毒素外子 (PE) 是替代拼接的外子,通过NMD.引发mRNA降解.
研究的目的:
- 审查PE拼接在基因调节中的作用.
- 讨论在疾病状态中对PEs的错误调节.
- 探索PE对调节基因表达的治疗潜力.
主要方法:
- 关于PE拼接和NMD的当前文献的综述.
- 分析RNA测序数据策略及其对理解PE功能的影响.
- 检查与PE调节错误相关的与疾病相关的基因表达模式.
主要成果:
- PE拼接是调节mRNA稳定性和丰富性的内生机制.
- 错误调节PE拼接有助于各种疾病状态.
- 对于特定序列的治疗干预来说,PEs提供了一个新的目标.
结论:
- PE拼接是基因表达的一个关键调节机制.
- 功能障碍的PE拼接与疾病的发病有关.
- 准PE拼接为遗传和其他疾病提供了一个有前途的治疗途径.
相关概念视频
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
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
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
What is Gene Expression?
8.4K
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
8.4K
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
RNA Editing
8.9K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
8.9K


