在固体瘤中,AEP通过DDX3X裂变促进异常RNA剪接
The Journal of clinical investigation
|February 1, 2024
概括
在固体瘤中异常RNA剪接是由阿斯巴拉金内酶 (AEP) 促进的. 瘤微环境激活AEP,它通过DDX3X改变RNA剪接,表明AEP是治疗点.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 生物化学 生物化学
背景情况:
- 异常的替代拼接 (AS) 在癌症中很常见.
- 身体突变和RNA结合蛋白 (RBPs) 与AS和恶性瘤有关.
- 驱动癌症相关AS的上游机制在很大程度上是未知的.
研究的目的:
- 确定调节固体瘤异常替代拼接的上游机制.
- 阐明阿斯巴拉金内酶 (AEP) 在与癌症相关的AS中的作用.
- 为了研究AEP,DDX3X和瘤进展之间的功能联系.
主要方法:
- 在瘤微环境条件下研究了阿斯巴拉金内酶 (AEP) 的活性.
- 使用过氧诱导因子1-alpha (HIF1A) 的依赖性试验.
- 通过AEP检查了RNA螺旋酶DDX3X的裂变.
- 分析了DDX3X核保留及其与拼接机械的相互作用.
- 在癌细胞中评估AS事件.
主要成果:
- 瘤的环境因素 (氧气/营养缺乏) 以依赖HIF1A的方式激活AEP.
- 激活的AEP可以分裂DDX3X,促进其核保留.
- 核DDX3X与剪接机械相互作用,在癌细胞中诱导异常AS事件.
- 依赖AEP的AS有助于固体瘤的进展.
结论:
- 阿斯巴拉金内酶 (AEP) 在促进固体瘤中异常RNA拼接方面发挥着关键作用.
- 由瘤微环境因素激活AEP驱动AS通过DDX3X裂变和核保留.
- 准依赖AEP的异常RNA拼接级联为固体瘤提供了潜在的治疗策略.
相关概念视频
RNA Splicing
56.4K
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...
56.4K
Alternative RNA Splicing
21.2K
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...
21.2K
RNA Editing
9.0K
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...
9.0K
Pre-mRNA Processing: RNA Splicing
5.2K
5.2K
Chromatin 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
Exon 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


