在人类细胞中对转录启动和促进者-近端暂停的平衡动态的基于模型的表征
Yixin Zhao1, Lingjie Liu1,2, Rebecca Hassett1
1Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Nucleic acids research
|October 27, 2023
概括
转录启动和RNA聚合酶 (RNAP) 暂停是基因表达的关键步骤. 我们的模型显示,暂停逃逸通常是限制速率的,并且固态障碍显著影响了元动物中的启动速率.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 计算生物学 计算生物学
背景情况:
- 转录启动和RNA聚合酶 (RNAP) 暂停是metazoan基因表达的关键速度限制步骤.
- 这些过程发生在物理接近的DNA位点,并可以通过固态相互作用相互影响.
研究的目的:
- 研究转录启动和RNAP暂停逃逸的动态.
- 开发一个模型,共同描述这些动力学和新生的RNA测序数据.
- 评估细胞变异性对暂停部位和固体阻碍对转录的影响.
主要方法:
- 开发一种概率模型用于转录启动,暂停逃逸和延长动力学.
- 基因表达动态的统计建模和模拟.
- 分析新生的RNA测序数据以估计动态速率.
主要成果:
- 开发的模型准确地估计了转录启动率和暂停逃逸率.
- 暂停逃逸通常是基因表达的速度限制步骤.
- 暂停RNAP的固体阻碍可以大大降低转录启动率.
结论:
- 概率模型为分析转录动态提供了一个强大的框架.
- 了解休息逃逸和硬质障碍对于理解基因表达调节至关重要.
- 免费使用的软件有助于在该领域进行进一步的研究.
相关概念视频
Transcription Elongation Factors
10.9K
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...
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...
10.9K
Bacterial Transcription
28.3K
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:
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
28.3K
Transcription Initiation
16.5K
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...
16.5K
RNA Polymerase II Accessory Proteins
9.2K
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...
9.2K
Transcription Attenuation in Prokaryotes
15.3K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
15.3K
Transcription in Prokaryotes
69
Transcription is a highly regulated process that converts genetic information into RNA molecules. The transcription cycle is divided into three key stages: initiation, elongation, and termination, each driven by specific molecular mechanisms.Initiation of TranscriptionIn bacteria, transcription begins when the RNA polymerase core enzyme associates with a sigma factor to form a holoenzyme. For example, the E. coli sigma factor called σ70 forms a holoenzyme, which recognizes the -10 (Pribnow...
69


