# Yeast Ribosome Biogenesis

> **NIH NIH R01** · CARNEGIE-MELLON UNIVERSITY · 2024 · $40,112

## Abstract

PROJECT SUMMARY/ABSTRACT
 Ribosomes are complex ribonucleoprotein particles that catalyze protein synthesis in almost all cells in
nature. The long-term goal of this project is to understand how the 80 proteins and four rRNAs comprising
eukaryotic ribosomes are assembled in vivo. We use the yeast Saccharomyces cerevisiae to facilitate molecular
genetic approaches, and cultured Hela cells to enable us to visualize the nucleolus, the cellular compartment
where ribosomes are made.
 Production of ribosomes is tightly linked to cell growth and proliferation. Consequently, dysregulation of
ribosome biogenesis and nucleolar integrity is linked to many diseases such as cancer, neurodegenerative
diseases, or developmental disorders. Because pathways of ribosome biogenesis are very conserved, our
studies in yeast will help understand mechanisms of regulation and dysregulation of ribosome production in
humans.
 Ribosome biogenesis requires a dynamic series of remodeling steps in which protein and RNA interactions
are established and reconfigured. These steps are made more efficient and more accurate by the activities of
more than 200 assembly factors present in nascent yeast ribosomes, which are required for their assembly, and
conserved across eukaryotes.
 To enable in-depth studies of mechanisms driving ribosome assembly, we focus on one interval: just prior to,
during, and immediately after exit of large ribosomal subunit precursors from the nucleolus into the nucleoplasm.
During this stage, several domains of ribosomal RNA are rearranged, numerous assembly factors complete their
functions and exit from pre-ribosomes, and new assembly factors enter the particles. We want to learn how these
dynamic remodeling steps are powered forward by energy-consuming assembly factors present at this stage.
 We are also investigating interconnections between ribosome assembly and the nucleolus, the prominent
biomolecular condensate thought to be formed through multivalent interactions between pre-ribosomes and
other nucleolar components. However, it is not clear exactly how ribosome assembly creates a nucleolus, nor
how material properties of the nucleolus enable efficient ribosome assembly.
 We propose experiments to address the following questions: (1) How do the RNA helicases/ATPases Drs1,
Has1, Dbp10, and Spb4 power maturation of pre-60S subunits during mid to late nucleolar stages of assembly?
(2) How does the structure and composition of pre-ribosomes enable them to be retained in the nucleolus? (3)
How does ribosome assembly contribute to the morphology and fluidity of the nucleolus?

## Key facts

- **NIH application ID:** 11096303
- **Project number:** 3R01GM028301-42S1
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** JOHN L. WOOLFORD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,112
- **Award type:** 3
- **Project period:** 1980-08-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11096303

## Citation

> US National Institutes of Health, RePORTER application 11096303, Yeast Ribosome Biogenesis (3R01GM028301-42S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11096303. Licensed CC0.

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