# Uncovering novel players in nucleolar organization and function

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $328,000

## Abstract

PROJECT SUMMARY
The nucleolus is one of the largest membraneless cellular organelles, responsible for ribosomal RNA (rRNA)
transcription, rRNA processing, and ribosome assembly. Nucleolar size and number are often correlated with
protein synthesis rate and proliferative capacity of a cell. Seminal studies have shown that increased nucleolar
size and number are common features of many cancers and that nucleolar defects are associated with
neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. Nevertheless, fundamental
information is still lacking on the molecular players and mechanism that control the dynamic assembly and
activity of the nucleolus in health and disease.
We identified a novel nucleolar protein named ZNF692 that is necessary to maintain nucleolar integrity and
activity. Knocking down ZNF692 resulted in abnormal ring-like nucleolar morphology, as well as compromised
protein synthesis. Our preliminary results indicate that ZNF692 interacts with multiple nucleolar proteins,
including NPM1, as well as rRNA processing and ribosome assembly factors. Our hypothesis is that ZNF692
assembles a hub for ribosome biogenesis in the nucleolus by simultaneously recruiting pre-rRNA, ribosomal
proteins, and ribosome biogenesis factors. We will define the molecular mechanism regulated by ZNF692 in
ribosome production (Aim 1). We will define the domains of ZNF692 that regulate nucleolar integrity and activity
(Aim 2). We will then determine how ZNF692 may regulate nucleolar assembly and dynamics (Aim 3). Our work
has the potential to provide fundamental data on the mechanisms and key regulators of nucleolar activity and
could become the basis for the development of novel approaches to alter nucleolar activity in diseased cells.

## Key facts

- **NIH application ID:** 10419813
- **Project number:** 1R01GM145744-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Maralice Conacci-Sorrell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $328,000
- **Award type:** 1
- **Project period:** 2022-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419813

## Citation

> US National Institutes of Health, RePORTER application 10419813, Uncovering novel players in nucleolar organization and function (1R01GM145744-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10419813. Licensed CC0.

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