The role of mRNA 5' end capping in the transcriptional regulation of gene expression in eukaryotic cells.

mRNA 5 末端加帽在真核细胞基因表达转录调控中的作用。

• 批准号: 2098601
• 金额: --
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2098601
• 关键词: role; mRNA; end; capping; transcriptional

The 5' RNA m7G cap is an essential modification of the RNA Polymerase II-dependent (Pol II) transcripts. An efficient mRNA capping is crucial for mRNA stability as it protects the RNA from 5'-3' degradation. The cap functions also as a platform for the Cap Binding Complex (CBC) which is essential for cellular RNA metabolism including nuclear export, degradation, and translation. Although the m7G cap has a crucial function in the mRNA biogenesis, very little is known about its direct role in transcription and ultimately, in gene expression. Previous reports indicate that defects in mRNA capping may affect the transition from transcription initiation to elongation or trigger premature transcription termination. Thus, the project will investigate in the model organism Saccharomyces cerevisiae how the mRNA cap, the capping enzymes and the capping process regulate transcription and RNA synthesis in eukaryotic cells. The student will employ chromatin immunoprecipitation (ChIP-seq) analysis to test genomic positions of Pol II phosphoisoforms as well as RNA analyses of steady-state (RNA-seq and direct RNA-seq) and nascent RNA (4tU RNA-seq) in cap-deficient cells. These approaches will provide a comprehensive analysis of how m7G cap and the capping impact nuclear RNA biology in eukaryotic cells. The outcomes of this project will reveal if and how RNA cap is related to 5'-3' co-transcriptional degradation and will define a correlation between capping, transcription progression and transcription termination of Pol II-transcribed genes.

5' RNA m7G帽是RNA聚合酶II依赖（Pol II）转录本的重要修饰。有效的mRNA capping对mRNA的稳定性至关重要，因为它可以保护RNA免受5‘-3’降解。帽还作为帽结合复合体（CBC）的平台，这对于细胞RNA代谢包括核输出，降解和翻译至关重要。尽管m7G帽在mRNA的生物发生中起着至关重要的作用，但人们对其在转录和最终基因表达中的直接作用知之甚少。先前的报道表明，mRNA capping缺陷可能影响转录起始到延伸的转变或触发转录过早终止。因此，该项目将在模式生物酿酒酵母中研究mRNA盖帽、盖顶酶和盖顶过程如何调节真核细胞中的转录和RNA合成。该学生将使用染色质免疫沉淀（ChIP-seq）分析来测试Pol II磷酸异构体的基因组位置，以及在帽缺陷细胞中对稳态（RNA-seq和直接RNA-seq）和新生RNA （4tU RNA-seq）进行RNA分析。这些方法将全面分析m7G帽和帽盖如何影响真核细胞中的核RNA生物学。该项目的结果将揭示RNA帽是否以及如何与5‘-3’共转录降解相关，并将定义帽盖，转录进展和转录终止之间的相关性Pol ii转录基因。