How does the nucleolus safeguard ribosome production during meiosis?

核仁如何在减数分裂过程中保护核糖体的产生？

• 批准号: 2882597
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2882597
• 关键词: How; does; nucleolus; safeguard; ribosome

Ribosome biogenesis is a fundamental and complex cellular process that involves the synthesis, assembly and export of ribosomal (r)RNAs and proteins into functional ribosomes. This process is differentially regulated in different cellular contexts. This PhD project will investigate the mechanisms by which mammalian cells may regulate ribosome production to protect their rDNA loci from nonallelic exchanges during meiosis. The aim is to study the importance of TEX12, a component of the meiosis-specific synaptonemal complex, and other regulatory co-factors in the early stages of ribosome assembly and pre-rRNA processing, which may be controlled or inhibited at meiosis onset.Specifically, I aim to understand the links between early pre-rRNA processing steps and ribosome biogenesis shutdown during meiosis. Pre-rRNA processing and maturation involves a series of endonucleolytic and exonucleolytic cleavage steps, and while most of the enzymes are known, endonucleases executing the early cleavage steps remain un-identified. During the course of my project, I aim to identify the enzyme cleaving at the first of the early pre-rRNA cleavage sites (A') and to clarify the role of UTP23, a candidate enzyme that has been proposed to cleave at site A0. I plan to do this via a combination of approaches - by altering the expression levels of regulatory co-factors and by using an artificial snoRNA designed to block cleavage at the A' or A0 cleavage site to capture the enzyme at its respective site of action.

核糖体生物发生是一个基本而复杂的细胞过程，涉及核糖体（r）RNA和蛋白质的合成，组装和输出到功能性核糖体。这一过程在不同的细胞环境中受到不同的调节。这个博士项目将研究哺乳动物细胞可能调节核糖体产生的机制，以保护其rDNA位点在减数分裂过程中不受非等位基因交换的影响。目的是研究TEX 12的重要性，减数分裂特异性联会复合体的一个组成部分，和其他监管辅助因子在核糖体组装和前rRNA加工的早期阶段，这可能是控制或抑制在减数分裂onset.Specifically，我的目标是了解早期前rRNA加工步骤和核糖体生物合成关闭减数分裂过程中的联系。前rRNA加工和成熟涉及一系列内切核酸和外切核酸切割步骤，虽然大多数酶是已知的，但执行早期切割步骤的内切核酸酶仍然未被鉴定。在我的项目过程中，我的目标是确定在早期前rRNA切割位点（A '）的第一个切割的酶，并澄清UTP 23的作用，UTP 23是一种被提议在位点A0切割的候选酶。我计划通过多种方法的组合来实现这一点-通过改变调节辅因子的表达水平，并通过使用人工snoRNA来阻断A'或A0切割位点的切割，以在其各自的作用位点捕获酶。