修复,删除和关闭:这一切都取决于RNA聚合酶II的普遍性
1Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
Cell
|March 24, 2020
概括
在RNA聚合酶II上单个氨酸残留的ubiquitylation作为主开关. 这一过程调节了转录,蛋白质降解和DNA损伤后的DNA修复.
科学领域:
- 分子生物学
- 生物化学
- 遗传学
背景情况:
- DNA损伤会触发细胞反应以维持基因组的完整性.
- RNA聚合酶II是基因转录的核心,并受到监管修改.
- 无处不在是一种关键的翻译后修饰,它调节了蛋白质的命运和功能.
研究的目的:
- 阐明在DNA损伤后RNA聚合酶II调节中无处不在的作用.
- 确定针对无处不在的特定氨酸残留物.
- 了解这种修改如何影响转录,蛋白质稳定性和DNA修复.
主要方法:
- 局部定向突变,以改变RNA聚合酶II上的特定氨酸残留物.
- 生物化学测试以评估无处不在的水平.
- 对基因转录率的分析.
- 对RNA聚合酶II降解途径的研究.
- 研究转录合核酸切除修复 (TC-NER) 的效率.
主要成果:
- 在RNA聚合酶II上对特定的lysine残留物进行ubiquitylation被确定为一个关键事件.
- 这种修改作为一个主开关, 协调多个细胞过程.
- 观察到调节的转录,受控的RNA聚合酶II降解和高效的TC-NER.
结论:
- 单残留RNA聚合酶II的无处不在是一种关键的调节机制.
- 这种修改整合了对DNA损伤的反应,影响了转录和修复.
- 这些发现为基因表达和基因组维护的动态调节提供了洞察力.
相关概念视频
Eukaryotic RNA Polymerases
26.5K
RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
All three eukaryotic RNAPs require specific transcription factors, of which the...
26.5K
Eukaryotic RNA Polymerases
8.9K
8.9K
Transcription Initiation
19.6K
Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
The promoters and enhancers and their accessory proteins allow tight regulation of...
19.6K
mRNA Stability and Gene Expression
6.4K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
6.4K
Nuclear Export of mRNA
8.5K
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...
8.5K
RNA Polymerase II Accessory Proteins
10.6K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
10.6K


