非编码RNA调节DNMT3A的机制
Jonathan E Sandoval1,2, Nancy V N Carullo3, Aaron J Salisbury3
1Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, 93106-9510, USA.
Epigenetics & chromatin
|March 28, 2025
概括
调节性RNA,如Fos ecRNA,可以直接抑制DNA甲基转移酶3A (DNMT3A) 的活性. 这种基于RNA的调节在控制DNA甲基化模式方面发挥着主导作用,特别是在调节性RNA丰富的地方.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
背景情况:
- 通过DNA甲基转移酶3A (DNMT3A) 进行新型DNA甲基化对于基因表达调节至关重要.
- DNMT3A活动是由基因素尾巴和调节蛋白调节的,涉及表观遗传机制之间的交叉声交换.
- 以前的研究表明,Fos染色体外RNA (ecRNA) 抑制神经元中的DNMT3A.
研究的目的:
- 研究Fos ecRNA在调节DNMT3A活动中的作用.
- 了解调节蛋白和基因质尾巴如何影响这种RNA介导的调节.
- 描述Fos ecRNA和DNMT3A之间的相互作用.
主要方法:
- 在皮层神经元中对Fos ecRNA和mRNA相关性的单细胞分析.
- 生物化学试验用于研究Fos ecRNA与DNMT3A的结合.
- 在体外实验中使用合成素H3尾巴和多核细胞体进行实验.
主要成果:
- Fos ecRNA 和 mRNA 水平在神经元中相互关联,表明协调调节.
- 福斯ecRNA以独立于序列的方式抑制DNMT3A活动.
- Fos-1 ecRNA 结合了 DNMT3A 四聚体接口,而 DNMT3L 可以恢复因突变破坏的抑制.
- 调节性RNA在调节DNMT3A活动中发挥着主导作用,即使在质子H3尾和多核细胞体中也是如此.
结论:
- 支持一个短调节RNA与DNMT3A非特异结合的模型.
- 调节性RNA在控制DNMT3A在特定基因组部位的催化活性方面发挥着主导作用.
- 这突出了基于RNA的表观遗传调节的重要机制.
相关概念视频
01:23Types of RNA
Overview
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 the regulation of 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...
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 the regulation of 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...
01:53RNA Stability
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...
02:41Chromatin Structure Regulates pre-mRNA Processing
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...
02:24Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
01:20Types of RNA
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...
01:23Regulation 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...