# Novel regulatory networks driving human ribosome biogenesis

> **NIH NIH R35** · YALE UNIVERSITY · 2020 · $627,470

## Abstract

Project Summary/Abstract
Over the last 15 years there has been an explosion in the number of recognized human genetic diseases of
making ribosomes, the ribosomopathies, most of which are inherited conditions. Despite the clear impact of
abnormalities in ribosome biogenesis on human disease, ribosome biogenesis in human cells is just beginning
to be investigated and elucidated. Key challenges now are to pinpoint how ribosomes are made in human
cells, to define how this critical process is regulated in different tissues and diverse cell types throughout
embryonic development, and to probe how failures in this process lead to the human diseases of making
ribosomes.
As one novel approach to better probe the mechanisms underlying how ribosomes are made in human cells,
we have successfully developed a unique, highly-quantitative and image-based cellular assay that reports
nucleolar dysfunction (Cell Reports 2018). We have conducted a genome-wide siRNA screen in near-diploid
MCF10A human breast epithelial cells to identify cellular proteins that change nucleolar number. This screen
was the first RNAi campaign to use nucleolar number as an endpoint, and the first screen of its type carried out
in a human cell line other than Hela cells. This unbiased screening approach revealed many new cellular
proteins (the “hits”) not previously connected to making ribosomes.
We have obtained and successfully validated both nucleolar and non-nucleolar hits, prompting the hypothesis
that the non-nucleolar proteins are novel indirect regulators of ribosome biogenesis in human cells. With
tailored technological strategies, we will further define the role of a subset of the hits in ribosome biogenesis in
human tissue culture cells, shedding light on unique regulatory pathways. In addition, we will link them to a
critical requirement in embryonic development using Xenopus tropicalis as a model system. Once looked upon
as a “housekeeping” organelle, our work will highlight the nucleolus as a significant contributor to human
genetic disease and congenital malformations.

## Key facts

- **NIH application ID:** 9900834
- **Project number:** 5R35GM131687-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Susan J Baserga
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $627,470
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900834

## Citation

> US National Institutes of Health, RePORTER application 9900834, Novel regulatory networks driving human ribosome biogenesis (5R35GM131687-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900834. Licensed CC0.

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