在患有神经认知障碍的临床人群中,RNA修饰系统的失调
Helen M Knight1, Merve Demirbugen Öz2, Adriana PerezGrovas-Saltijeral1
1Division of Cells, Organisms and Molecular Genetics, School of Life Sciences, University of Nottingham, Nottingham, UK.
Neural regeneration research
|October 31, 2023
概括
包括N6腺 (m6A) 和C5细胞 (m5C) 在内的RNA甲基化对大脑功能至关重要. 这些表皮转录体标记的破坏与阿尔茨海默氏症和智力障碍等神经认知障碍有关.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 经转录学,即对RNA修饰的研究,对于理解疾病机制至关重要.
- N6腺 (m6A) 和C5细胞 (m5C) 甲基化发生在各种RNA类型中.
- RNA结合蛋白 (写入器,读取器,擦拭器) 调节这些修饰和生理过程.
研究的目的:
- 审查累积的证据,将m6A和m5C甲基化系统与神经认知障碍联系起来.
- 突出特定基因和蛋白质在智力发育障碍和神经退行性疾病中的作用.
- 探索改变脑组织中的RNA甲基化对阿尔茨海默病,创伤性脑损伤和莱维体疾病等疾病的影响.
主要方法:
- 关于RNA甲基化和神经认知障碍的现有文献的综述.
- 分析与智力障碍相关的遗传突变.
- 检查与神经退行性疾病相关的大脑组织中的蛋白质表达变化.
主要成果:
- 在FMR1,METTL5,NSUN2,NSUN3,NSUN5,NSUN6,THOC2,THOC6和ALYREF中的突变与智力发育障碍有关.
- 大脑组织中NSUN6,NSUN7和ALYREF的改变表达与阿尔茨海默病和创伤性脑损伤有关.
- 在Lewy体疾病,阿尔茨海默病和帕金森病中观察到m6A读者/反读者蛋白和改性RNA丰度的变化.
结论:
- RNA甲基化系统的失调有助于神经元和突触功能障碍,这是神经认知障碍的基础.
- 准RNA修饰系统为神经再生提供了潜在的治疗策略.
相关概念视频
02:23RNA 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
01:53RNA Stability
33.6K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.6K
02:31Nuclear Export of mRNA
7.7K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K
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
01:37Neural Regulation
39.5K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.5K
01:28Biosynthesis of Nucleic Acids
56
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
56