# Structure/Function of Transcription Complex Regulation

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $750,786

## 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 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. Understand-
ing how regulators promote or inhibit these different conformations will provide key basic knowledge essential
to guide the rational manipulation of regulators for antimicrobials or gene therapies. Knowledge gained about
model bacterial systems also facilitates understanding of highly conserved mechanisms of transcription in
humans. Additionally, bacterial RNA polymerase is a known target of antibiotics, and knowledge about its
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 assists
RNA folding, of the role of H-NS family nucleoprotein filaments in stimulation of pausing and termination
during transcriptional silencing, and of interaction of RNA polymerase with the pioneering ribosome in a
complex called the expressome. The specific aims of the project are to (i) elucidate steps in pausing, termina-
tion, and RNA folding and roles of key RNAP modules; (ii) define structures, patterns, and elongation complex
interactions of H-NS family nucleoprotein filaments; and (iii) determine when the expressome forms and how
it functions during transcript elongation. This integrated research will help build a new understanding of tran-
scriptional regulation by defining how pause and termination signals change elongation complex structure and
activity dynamically and how chromosome structure and translational coupling modulate elongation complex
activ...

## Key facts

- **NIH application ID:** 10187584
- **Project number:** 5R01GM038660-35
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Robert Landick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $750,786
- **Award type:** 5
- **Project period:** 1987-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187584

## Citation

> US National Institutes of Health, RePORTER application 10187584, Structure/Function of Transcription Complex Regulation (5R01GM038660-35). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10187584. Licensed CC0.

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