# UNDERSTANDING THE ROLES OF RNA POLYMERASE I IN TRANSCRIPTION AND BEYOND

> **NIH NIH R35** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $351,512

## Abstract

Eukaryotic cells deploy at least three multisubunit, DNA-dependent RNA polymerases to
express the robust variety of RNAs required for cell survival and proliferation. In contrast to
prokaryotic cells which express a single RNA polymerase, eukaryotic RNA polymerases have
evolved into specialized cellular roles. RNA polymerase I (Pol I) synthesizes the majority of
ribosomal RNA, Pol II synthesizes messenger RNA and most regulatory RNAs, whereas Pol III
synthesizes transfer RNA and the 5S ribosomal RNA. While this "division of labor" among the
nuclear Pols has been appreciated for many years, substantial gaps in our understanding of the
functional divergence between the eukaryotic RNA polymerases remain. How do the enzymatic
properties of these enzymes differ? How do these functional differences influence regulation of
transcription by associated transcription factors? How do divergent enzymatic properties of the
Pols impact their unique cellular roles? The answers to these questions are fundamentally
important for understanding eukaryotic biology.
 It is well established that the rate of ribosome synthesis is proportional to the rates of cell
growth and proliferation. As a consequence, several labs around the world seek novel inhibitors
of ribosome synthesis as potential anticancer chemotherapy agents. Since transcription of the
ribosomal DNA by Pol I is the first, rate-limiting step in ribosome synthesis, Pol I has emerged
as a key target for the development these inhibitors. In order to selectively inhibit one RNA
polymerase without affecting the others, it is crucial to understand the fundamental properties of
the enzymes as well as the cellular mechanisms by which the enzymes are controlled. Thus,
defining Pol I activity and its cellular roles has immediate translational value.
 By defining the landscape of eukaryotic transcription and the many cellular roles of Pol I, this
project will reveal answers to fundamental questions in evolutionary biology while informing
ongoing studies aimed at therapeutic targeting of ribosomal RNA synthesis. To reach these
goals, our lab has developed a robust platform of experimental approaches including
biochemical, biophysical, genetic, and genomic methodologies. We have pioneered the
development of both the experimental and analytical strategies required to rigorously and
thoroughly define the functional properties of RNA polymerase I. The overall goal of this project
is to leverage these experimental strengths to impact our overall understanding of eukaryotic
gene expression and to lay the foundation for ongoing and future studies aimed at therapeutic
inhibition of Pol I.

## Key facts

- **NIH application ID:** 10159609
- **Project number:** 1R35GM140710-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** David Alan Schneider
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $351,512
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159609

## Citation

> US National Institutes of Health, RePORTER application 10159609, UNDERSTANDING THE ROLES OF RNA POLYMERASE I IN TRANSCRIPTION AND BEYOND (1R35GM140710-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159609. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*