How does the nucleolus safeguard ribosome production during meiosis?

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rna和蛋白质的合成、组装和输出到功能性核糖体中。这一过程在不同的细胞环境中受到不同的调节。该博士项目将研究哺乳动物细胞在减数分裂期间调节核糖体产生以保护其rDNA位点免受非等位基因交换的机制。目的是研究减数分裂特异性突触复合体的组成部分TEX12和其他调节辅助因子在核糖体组装和前rrna加工的早期阶段的重要性，这些因子可能在减数分裂开始时受到控制或抑制。具体来说，我的目标是了解早期pre-rRNA加工步骤与减数分裂期间核糖体生物发生关闭之间的联系。Pre-rRNA的加工和成熟涉及一系列核内裂解和核外裂解裂解步骤，虽然大多数酶是已知的，但执行早期裂解步骤的内切酶仍未确定。在我的项目过程中，我的目标是确定在早期pre-rRNA切割位点（A'）的第一个切割酶，并阐明UTP23的作用，这是一种被提出在A0位点切割的候选酶。我计划通过多种方法来实现这一目标——通过改变调节辅助因子的表达水平，并通过使用人工snoRNA来阻断a '或A0切割位点的切割，从而在其各自的作用位点捕获酶。

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.