# A detailed exploration of the physical and biochemical properties that contribute to RNA thermometer activity

> **NIH NIH R15** · OHIO UNIVERSITY ATHENS · 2020 · $447,390

## Abstract

Project Summary
Shigella is a genus of pathogenic bacteria responsible for over 165 million infections and 1.1 million deaths each
year. Our recent studies have demonstrated that RNA thermometers (RNATs) control the expression of several
virulence-associated genes in this important pathogen. The current definition of an RNAT is a simple one: a
temperature-sensitive structural element located within the 5' UTR of the regulated transcript that blocks
ribosomal binding at non-permissive temperatures. Defined as the minimal sequence unit sufficient to confer
such regulation, it is generally assumed that the mechanism of RNAT-mediated regulation is conserved and that
it is independent of additional cellular factors. Work by us and others have drawn this simple definition into
question. It has become abundantly clear that RNATs are a diverse collection of ribo-regulators, differing in size,
structure, location within a regulated transcript and the cellular processes that they control. Our central
hypothesis is that the structure and regulatory activity of different RNATs respond differently to uniform changes
in temperature, and that such responses are influenced by additional sequences within the 5' UTR and/or binding
of rRNA. Such potential complexities of RNAT activity have not been investigated. To this end, the overall goal
of this study is to complete comprehensive genetic and biochemical characterizations of four unique virulence-
associated RNATs located within virulence-associated genes of S. dysenteriae. The overall goal of this
application will be achieved in three specific aims. Aim 1 will measure the differential effect of temperature on
the structure of different RNATs and identify the impact of additional 5' UTR sequences and rRNA on such
responses. Aim 2 will determine the differential effect of temperature on ribosomal binding to different RNATs
and measure the impact of additional 5' UTR sequences on this response. Aim 3 will characterize the impact of
each RNAT on specific S. dysenteriae virulence-associated processes. The multi-disciplinary analysis of four
unique RNATs from a single bacterial pathogen is a powerful and novel approach with the strong potential to
contribute foundational knowledge to the field. In addition, the proposed studies will make a significant
contribution to the current understanding of Shigella virulence.
The complementary skill sets of the PI (Murphy; RNATs, bacterial pathogenesis) and Co-Investigator (Hines;
RNA structure-function, biochemistry) ideally position this team to successfully complete this multidisciplinary
study, a study that will allow the research training of twelve undergraduate students, two graduate students
and three medical student researchers.

## Key facts

- **NIH application ID:** 9964393
- **Project number:** 1R15AI147238-01A1
- **Recipient organization:** OHIO UNIVERSITY ATHENS
- **Principal Investigator:** ERIN R MURPHY
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $447,390
- **Award type:** 1
- **Project period:** 2020-03-09 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964393

## Citation

> US National Institutes of Health, RePORTER application 9964393, A detailed exploration of the physical and biochemical properties that contribute to RNA thermometer activity (1R15AI147238-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9964393. Licensed CC0.

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