How does the nucleolus safeguard ribosome production during meiosis?

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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.