由转移RNA修饰损失引起的神经疾病:它们分子致病的共同点
Takeshi Chujo1, Kazuhito Tomizawa1
1Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Journal of molecular biology
|March 11, 2025
概括
人类转移RNA (tRNA) 修改对于稳定性和功能至关重要. 这些修改中的干扰会导致tRNA模式病,导致神经退行症和记忆障碍等神经系统疾病.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 神经科学是一个神经科学.
背景情况:
- 人类转移RNA (tRNA) 经历了46种不同的转录后修饰.
- 这些修改对于tRNA结构完整性,生化稳定性和准确的子-子相互作用至关重要.
- 在tRNA修饰酶和相关蛋白质的缺陷导致tRNAmodopathies,一类疾病.
研究的目的:
- 阐明人类tRNA修饰的分子功能.
- 编制人类tRNA修改作者和相关的神经tRNA模式病的综合清单.
- 审查神经性tRNA模式病变背后的致病机制.
主要方法:
- 文献综述和现有数据的汇编.
- 分子功能和疾病关联的分析.
- 综合有关tRNA修饰途径和神经影响的信息.
主要成果:
- 已经确定了80多个人类tRNA修饰编写者和众多神经tRNA模式病.
- 丢失的tRNA修改可以导致tRNA不稳定,改变解码,或有毒的tRNA片段.
- 这些分子缺陷通过失调的蛋白质稳定或通过转化缺陷的记忆障碍导致神经退行.
结论:
- 神经组织特别容易受到tRNA修饰缺陷的影响.
- 越来越多的证据支持神经性tRNA模式病变的特定致病机制.
- 需要进一步的研究,以充分理解tRNA修饰在神经系统中的作用,并制定治疗策略.
相关概念视频
Translation
141.7K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
141.7K
Nuclear Export of mRNA
7.6K
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...
7.6K
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
Transfer RNA Synthesis
11.9K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
11.9K
Types of RNA
5.7K
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
RNA Performs Diverse...
5.7K
Alternative RNA Splicing
21.1K
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...
21.1K


