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Content archived on 2024-05-29

A focus on degradation of ribosomal RNAs by the TRAMP/exosome RNA surveillance machinery

Final Activity Report Summary - RRNA SURVEILLANCE (A focus on degradation of ribosomal RNAs by the TRAMP/exosome RNA surveillance machinery)

Ribosomes, the large RNA-protein complexes that translate mRNA into protein in the cytoplasm of eukaryotic cells, are largely synthesized in a subnuclear compartment called the nucleolus. Synthesis of ribosomal RNA (rRNA) and ribosome assembly are tightly coordinately regulated and require the activity of more than 150 protein factors, underscoring the complexity of this process. Deregulation of steps in ribosome biogenesis is often associated with alterations in cell cycle, cell proliferation and cell growth and often contributes to increased susceptibility to cancer. Indeed, aberrant nucleolar morphology is often a hallmark for cancer cells. However, the molecular mechanism underlying the link between cancer and the activity of nucleolar proteins is largely unknown.

A detailed understanding of ribosome biogenesis and how it is regulated will help us comprehend the links found between ribosome assembly and cancer. The objectives of this study were to understand how and where in the cell the production of rRNA is monitored. The biggest achievement made during the funding period was to develop a technology that allows researchers to figure out where proteins interact with the RNA during the assembly of ribosomes. The project used this technology to generate a map of protein-RNA interactions in pre-ribosomes. The results of these studies are widely considered a breakthrough in the ribosome assembly field and will have long term impact on the field for years to come.