# Administrative Supplement: Structure/Function of Transcription Complex Regulation

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $126,508

## Abstract

Project Summary/Abstract
The long-term goal of this project is to define the interactions within transcription elongation complexes and
with regulators that cause and control pausing and termination by RNA polymerase. Pausing and premature
termination underlie many aspects of gene regulation in diverse prokaryotes and eukaryotes, including
transcription through chromatin and linkages to RNA maturation and translation. Both the basic mechanisms
of pausing and termination and the mechanisms by which regulators control pausing and termination depend
on poorly understood changes to interactions within the elongation complex. Many of these interactions
modulate conformational changes in RNA polymerase involving mobile modules including the clamp, trigger
loop, and lineage-specific insertions that must achieve particular conformations for efficient transcription.
Understanding how regulators promote or inhibit these different conformations in diverse bacteria will provide
key basic knowledge essential to guide the rational manipulation of regulators for antimicrobials or genetic
therapies. Knowledge gained about diverse bacterial systems also helps define highly conserved mechanisms of
transcription in humans. Additionally, bacterial RNA polymerases are known target of antibiotics, and
knowledge about their functional mechanisms will aid in identifying and characterizing new antibiotics.
 A combination of structural, biochemical, and genetic approaches will be used to characterize the interac-
tions in the elongation complex that mediate regulation. New methods for transcription assay by cryo-electron
microscopy, for single-molecule assay of RNA polymerase interactions with RNA structures, regulators, and
ribosomes, and for genome-scale analysis of chromatin structure and elongation complex regulation will be
developed. This combination of approaches will be used to understand connections among progress of the
elongation complex during transcription, the structure of bacterial chromatin, RNA folding, and RNA
translation. The work builds on recent discoveries of the structural basis by which RNA polymerase pauses, of
the role of H-NS family nucleoprotein filaments in stimulating pausing and termination during transcriptional
silencing, and of the different actions of the only universal transcription elongation regulator, NusG. The
specific aims of the project are to (i) integrate models of pausing and termination mechanisms across diverse
bacterial lineages; (ii) elucidate the molecular basis of pro- vs. anti-pausing and recruitment for NusGs and
paralogs; and (iii) link genome-scale regulation in vivo to the molecular basis of elongation complex structural
changes. This integrated research will help build a new understanding of transcriptional regulation by defining
how pause and termination signals change elongation complex structure and activity dynamically across
evolutionarily diverse microbes. The impact of these studies will be an improved unders...

## Key facts

- **NIH application ID:** 11094455
- **Project number:** 3R01GM038660-38S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Robert Landick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $126,508
- **Award type:** 3
- **Project period:** 1987-07-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11094455

## Citation

> US National Institutes of Health, RePORTER application 11094455, Administrative Supplement: Structure/Function of Transcription Complex Regulation (3R01GM038660-38S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11094455. Licensed CC0.

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