人类catechol-O-methyltransferase单基类型通过改变mRNA二次结构来调节蛋白质表达.
A G Nackley1, S A Shabalina, I E Tchivileva
1Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC 27599, USA.
概括
在Catechol-O-methyltransferase (COMT) 基因的同名变异影响蛋白质水平和活性,影响疼痛敏感性. 单个SNP而不是单个哈普类型对于理解COMT基因功能至关重要.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 神经科学是一个神经科学.
背景情况:
- 甲基转移酶 (COMT) 在调节神经递质水平方面起着至关重要的作用.
- COMT活动与疼痛感知,认知功能和情绪调节有关.
- 在COMT基因的遗传变异可以影响其酶活性和相关功能.
研究的目的:
- 调查常见的COMT基因单基因类型对COMT酶活性的功能影响.
- 确定COMT单元类型中同义和非同义变异的作用.
- 探索信使RNA结构和蛋白质表达水平之间的关系.
主要方法:
- 分析了三种常见的人类COMT基因单元型.
- 评估COMT酶活性不同类型之间的差异.
- 研究信使RNA局部干环结构的研究.
- 局部导向突变发生以改变RNA结构.
主要成果:
- 具有同义变化的哈普类型在COMT酶活性中表现出最显著的差异.
- 在具有更稳定的信使RNA干循环结构的平分类型中观察到减少的翻译蛋白水平.
- 蛋白质水平和活性的恢复是通过通过突变生成破坏稳定的RNA结构来实现的.
结论:
- 同名的遗传变异可以对蛋白质水平和活性产生重大功能影响.
- 传递 RNA 的二次结构在调节 COMT 蛋白质表达方面发挥着至关重要的作用.
- 哈普洛型分析,而不是单核酸多态分析,对于全面了解COMT基因变异至关重要.
相关概念视频
Mutations
Overview
Transfer RNA Synthesis
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...
RNA Editing
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...
Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
What is Gene Expression?
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 processed and...
Regulation of Expression at Multiple Steps
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 addition of a...


