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，涉及到核糖体RNA和蛋白质的合成、组装和输出到功能核糖体中。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在减数分裂过程中调节核糖体生产以保护其rDNA基因座免受非等位基因交换的机制。其目的是研究TEX12，减数分裂特异性联会复合体的一个组成部分，以及在核糖体组装和前rRNA加工的早期阶段可能被控制或抑制的其他调节辅助因子的重要性。具体地说，我的目的是了解早期前rRNA加工步骤和减数分裂过程中核糖体生物发生关闭之间的联系。前rRNA的加工和成熟涉及一系列内切和外切步骤，虽然大多数酶是已知的，但执行早期切割步骤的内切酶仍未确定。在我的项目过程中，我的目标是鉴定第一个早期前rRNA裂解位点(A‘)的酶，并澄清UTP23的作用，UTP23是一种已被提议在A0位点裂解的候选酶。我计划通过多种方法的组合来做到这一点--通过改变调控辅助因子的表达水平，以及通过使用旨在阻止A‘或A0裂解位点的裂解来捕获各自作用部位的酶的人造snoRNA。

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.