# Mechanism and Regulation of RNA Polymerase II Elongation

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $498,641

## Abstract

PROJECT SUMMARY
Transcription in eukaryotes requires RNA polymerase II (Pol II) to faithfully synthesize RNA relative to DNA
sequence. Pol II must also successfully negotiate obstacles within chromatin templates and coordinate
cotranscriptional events. Disruption of any of these processes may alter gene expression outcomes and
derange cellular growth or physiology. Pol II, like all multisubunit cellular RNA polymerases (msRNAPs),
contains an essential active site domain – the trigger loop (TL) – that participates in all basic nucleotide
addition cycle (NAC) functions. Changes to Pol II catalytic activity have the power to alter every phase of
transcription: initiation, elongation, termination, and cotranscriptional RNA processing. It is therefore likely that
evolution of Pol II function has involved complex trade-offs between the rate, efficiency and fidelity of these
processes. Structural, biochemical and genetic studies alike on Pol II from Saccharomyces cerevisiae have
enabled critical insight into eukaryotic transcription. The high conservation of the S. cerevisiae transcription
machinery and its amenability to a wide-range of experimental approaches make yeast uniquely suited to
decipher gene expression mechanisms. We leverage novel approaches from high-throughput quantitative
phenotyping, structural analysis of unique Pol II variants, and determination of Pol II-natural product
interactions to test existing, and generate new, models for Pol II function. Misregulation of gene expression is a
major contributor to human disease. Basic research into transcription mechanisms enables the defects in
transcription found in disease states to be better understood.

## Key facts

- **NIH application ID:** 9936203
- **Project number:** 5R01GM097260-10
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Craig Kaplan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $498,641
- **Award type:** 5
- **Project period:** 2011-08-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936203

## Citation

> US National Institutes of Health, RePORTER application 9936203, Mechanism and Regulation of RNA Polymerase II Elongation (5R01GM097260-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9936203. Licensed CC0.

---

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