IWS1在转录延长中的结构和功能
bioRxiv : the preprint server for biology
|September 5, 2025
概括
与SPT6 (IWS1) 相互作用,作为组织转录延长因子的支架. 它的无序区域使用短线性图案来招募和刺激RNA聚合酶II,揭示了一个新的调节机制.
科学领域:
- 分子生物学
- 基因调控
- 蛋白质的结构和功能
背景情况:
- 通过RNA聚合酶II进行转录延长是复杂的,涉及许多蛋白质因素.
- 在此过程中,Interacts与SPT6 (IWS1) 蛋白的精确分子作用尚未完全理解.
研究的目的:
- 阐明IWS1作为转录延长因子的分子机制.
- 研究IWS1内在无序区域和短线性动机 (SLiM) 在调节转录中的作用.
主要方法:
- 电子显微镜绘制转录延长复合体内的相互作用.
- 生物化学和功能测定以评估IWS1的招募和转录刺激.
- 识别相互影响的合作伙伴以及其他延伸因素的监管作用.
主要成果:
- IWS1利用其无序的C端区域中的SLiM与转录机械的多个组件相互作用,包括Pol II子单元 (RPB1,RPB2,RPB5),DSIF,SPT6和ELOF1.
- 通过RPB1和下游DNA调用IWS1,并通过RPB2和ELOF1进行转录刺激.
- IWS1充当支架,组织延长复合并保护其免受RECQL5的抑制,同时也与与核细胞结合的LEDGF相互作用.
结论:
- IWS1作为一个模块化的支架,通过SLiM介导的多价值相互作用来组织转录延长复合体.
- 这些发现突显了固有无序的蛋白质区域如何被重新利用,在基因表达中创建复杂的调节枢纽.
- 这项研究揭示了IWS1和相关因子在转录延长中的新相互作用和调节作用.
相关概念视频
Transcription Elongation Factors
11.1K
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...
11.1K
Transcription Initiation
16.7K
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...
16.7K
General Transcription Factors
5.5K
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...
5.5K
Bacterial Transcription
29.3K
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:
29.3K
Transcriptional Regulation: Riboswitches
113
Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
113
RNA Polymerase II Accessory Proteins
9.4K
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...
9.4K


