# RNA Polymerase I Associated Factors: Novel Targets in Cancer Therapy

> **NIH NIH F31** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $33,546

## Abstract

PROJECT SUMMARY/ABSTRACT
The regulation of ribosome biogenesis (RB) plays a central role in maintaining cellular homeostasis and
supporting cell growth. The rate-limiting step in this process is transcription of the ribosomal RNA genes by RNA
polymerase I (Pol I). Dysregulation of RB can contribute to pathologies such as cancer, cardiac hypertrophy, and
ribosomopathies. Further, many chemotherapeutic drugs inhibit either rDNA transcription or rRNA processing,
but have many off-target effects that limit their usefulness. Many pathways play a role in the regulation of rDNA
transcription. Two mammalian factors that are involved in this regulation are Polymerase Associated Factor 53
(PAF53) and PAF49. The purpose of this study is to determine the role(s) of PAF49 and 53 in rDNA transcription
and characterize the downstream physiological effects of directly inhibiting this process in both normal and
cancer cells. This will be an important comparison since normal cells arrest when rDNA is inhibited while cancer
cells die.
To rapidly degrade PAF49/53, a novel system that utilizes CRISPR/Cas 9 and an auxin inducible degron will be
used. This will allow us to carry out in vitro biochemical and “genetic” studies of PAF49/53 in mammalian cells.
Our published data demonstrates that PAF53 is required for rDNA transcription and cell proliferation. In addition,
the three domains of PAF53 are each necessary but not sufficient to support wild-type levels of cell growth. Our
lab has also defined a second DNA-binding domain in PAF53 that had not been discovered. This study will
expand upon the domain analysis of PAF53 and further characterize its DNA-binding activity. The work proposed
is significant as it will aid in further understanding the process of rDNA transcription by Pol I and the physiological
consequences of inhibiting this process, i.e. nucleolar stress and cell death. It will also contribute to the discovery
of novel drug targets that could be utilized in effective cancer treatments.
To complete the proposed research, I will be exposed to new techniques such as crosslinking mass
spectrometry, live-cell imaging, and chromatin immunoprecipitation. To improve my scientific communication
skills, I will attend and present at the OddPols, AACR and other national and local conferences, as well as attend
workshops on scientific writing. I will also prepare multiple manuscripts for publication. Further, I will take multiple
opportunities to gain teaching experience. I also will attend seminars and professional development workshops
to help extend my scientific purview beyond my field. These opportunities will allow me to network and engage
with fellow scientists in order to build connections for future collaborative projects. Overall, the training I will
receive during this fellowship will help prepare me to be a competitive postdoctoral candidate and a successful
independent research scientist.

## Key facts

- **NIH application ID:** 10151230
- **Project number:** 1F31CA250352-01A1
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Rachel McNamar
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,546
- **Award type:** 1
- **Project period:** 2021-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151230

## Citation

> US National Institutes of Health, RePORTER application 10151230, RNA Polymerase I Associated Factors: Novel Targets in Cancer Therapy (1F31CA250352-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10151230. Licensed CC0.

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