人类Pol III转录启动的结构性见解
在PubMed上查看摘要
概括
此摘要是机器生成的。研究人员发现了RNA聚合酶III (Pol III) 的启动-延长过渡机制. 这揭示了Pol III如何逃离促进体以重新启动必要的小RNA的转录.
科学领域
- 分子生物学
- 结构生物学
- 生物化学
背景情况
- RNA聚合酶III (Pol III) 使用经典促进剂转录必要的小RNA.
- 从Pol III预启动复合体 (PIC) 过渡到延伸复合体 (EC) 的机制仍然不太清楚.
- 之前的研究确定了Pol III PIC和EC的结构,但缺乏对启动-延长开关的洞察力.
研究的目的
- 阐明从Pol III启动到延长过渡的分子机制.
- 捕捉和描述人类Pol III转录复合物的中间状态.
- 了解转录泡,通用转录因子 (GTF) 分离和促进体逃逸的动态.
主要方法
- 对7个人类的Pol III转录复合体 (TCs) 的复合停止了U6促进体.
- 电子显微镜 (cryo-EM) 用于确定最初转录复合体 (ITC) 和EC的结构.
- 用KMnO4足迹分析结构重组和DNA-RNA混合动力学.
主要成果
- 在ITC-EC过渡期间,冷电磁结构显示了广泛的模块化重组.
- 转录泡扩张到TC5,然后突然从TC5崩到TC6随着GTF解离.
- 在TC5中,SNAPc和TFIIIB仍然与BRF2阻断模板DNA结合;混合转位触发GTF释放和泡崩.
结论
- 这项研究揭示了任何RNA聚合酶最早记录的启动延长过渡.
- 提供了对Pol III动态的分子见解,包括BRF2指收缩和促进体逃逸.
- 这些发现揭示了高需求的小RNA类型3促进者的Pol III重启机制.
相关概念视频
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...
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
RNA polymerase (RNAP) carries out DNA-dependent RNA synthesis in both bacteria and eukaryotes. Bacteria do not have a membrane-bound nucleus. So, transcription and translation occur simultaneously, on the same DNA template.
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
Initiation, which involves two specific sequences 10 and 35 base pairs upstream of the gene, which are called promoters.
Elongation, where the...
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...
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...
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...

