在5'UTRSHMT1中的G-四重复和i-动机结构调节基因表达
bioRxiv : the preprint server for biology
|December 15, 2025
概括
多发性硬化症 (MS) 研究在SHMT1基因中确定了G-四重复和i-动机结构. 这些DNA和RNA结构调节基因表达,为MS提供潜在的治疗点.
科学领域:
- 遗传学 遗传学 是一个
- 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:
- 多发性硬化症 (MS) 是一种致命的神经退行性疾病,没有有效的治疗方法.
- 基因失调,特别是DNA甲基化,与MS的进展有关.
- 准DNA和RNA二次结构为MS提供了一个潜在的治疗策略.
研究的目的:
- 调查DNA和RNA二次结构在MS中Serin基甲基转移酶1 (SHMT1) 调节中的作用.
- 描述SHMT1基因中的G-四重复 (GQ) 和i-动机 (iM) 结构.
- 探索这些结构作为MS治疗点的潜力.
主要方法:
- 在SHMT1 5'未翻译区域 (DNA) 和mRNA中识别和描述GQ和iM结构.
- 报告者基因测试用于评估GQ/iM结构对基因表达的影响.
- 在MS患者中分析SHMT1基因表达.
主要成果:
- 在SHMT1DNA5' UTR中发现了一种混合的3+1 GQ/iM结构.
- 在SHMT1mRNA中发现了平行GQ结构.
- 这些GQ/iM结构被证明可以抑制记者基因mRNA水平和蛋白质表达.
结论:
- 在SHMT1中,GQ/iM结构在调节其表达方面起着至关重要的作用.
- 这些结构代表了MS干预的潜在治疗目标.
- 针对这些结构的进一步研究可能会导致新的MS治疗方法.
相关概念视频
Riboswitches
9.5K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
9.5K
Translational Regulation
507
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
507
Combinatorial Gene Control
9.4K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
9.4K
Covalently Linked Protein Regulators
8.6K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.6K
Regulation of Expression at Multiple Steps
1.3K
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...
1.3K
Chromatin Structure Regulates pre-mRNA Processing
8.1K
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...
8.1K


