# Control of RNA polymerase I transcription initiation and elongation

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $319,413

## Abstract

Ribosome biosynthesis is intimately linked to the rates of cell growth and proliferation.
Transcription of the ribosomal DNA, mediated by RNA polymerase I (Pol I), is the first, rate-
limiting step in ribosome biosynthesis. Based on its critical role in cell biology and its recent
emergence as a therapeutic target, the overall goal of this project is to define the mechanisms
that control Pol I activity and orchestrate early steps in ribosome biosynthesis.
Eukaryotic RNA polymerases have specialized roles, and the three largest ribosomal RNAs are
synthesized uniquely by Pol I. There is growing interest in developing Pol I as a therapeutic
target for cancer, but to accomplish this goal, we must understand how the enzyme works and
how it is regulated. This project will deploy a series of biochemical strategies to define
enzymatic properties of Pol I and compare those properties to Pols II and III.
The ribosomal DNA locus is densely packed with Pol I transcription elongation complexes, and
the kinetics of transcription by these enzymes directly influence processing of the nascent
rRNA. Transcription elongation efficiency is influenced by trans-acting transcription elongation
factors, DNA template sequence, and metabolic status of the cell. To define how these complex
biochemical processes are orchestrated this project will use a blend of genetic, genomic,
biochemical and bioinformatic approaches to identify DNA sequences that control Pol I
transcription elongation in vitro and in vivo.
Many transcription factors that fine tune rRNA expression have been defined. Several of these
transcription factors are known to affect Pols I and II, often exhibiting very different effects on
the respective enzymes. To understand the principles by which gene expression is regulated
there is a need to define the mechanism by which transcription factors function. Pol I is an
excellent model enzyme for characterizing transcription factor function in detail.
The overall goal of this project, and the Schneider lab as a whole, is to move the field toward
mechanistic definition of ribosome biosynthesis. A detailed understanding of this process is
fundamentally important to cell biology. Furthermore, there is growing interest in developing
selective inhibitors of ribosome biosynthesis, with a focus on Pol I. Thus, there is a critical need
for a more complete, mechanistic definition of Pol I function.

## Key facts

- **NIH application ID:** 9981818
- **Project number:** 5R01GM084946-12
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** David Alan Schneider
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $319,413
- **Award type:** 5
- **Project period:** 2009-09-30 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981818

## Citation

> US National Institutes of Health, RePORTER application 9981818, Control of RNA polymerase I transcription initiation and elongation (5R01GM084946-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9981818. Licensed CC0.

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