# Molecular Determinants of Regulatory Hierarchy for Bacterial Small RNAs

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $317,205

## Abstract

PROJECT SUMMARY
Small RNAs (sRNAs) are numerous and carry out intricate regulatory mechanisms, yet their specific roles in
bacterial physiology and virulence remain by and large mysterious. Our previous work with two model E. coli
sRNAs, SgrS and RyhB, shed light on some of the roles played by sRNAs in bacterial physiology and stress
responses and uncovered novel molecular mechanisms of regulation. We showed that a single sRNA can
base pair with numerous mRNA targets, and promote the rapid degradation of these mRNAs, with important
consequences for key processes including sugar transport and metabolism (SgrS) and iron homeostasis
(RyhB). We defined a novel class of competitors, so-called “sponge” RNAs that bind and modulate the ability of
sRNAs to regulate their mRNA targets. In the current proposal, we build on these preliminary studies to
address several questions with broad relevance to the sRNA field. 1) What kinetic parameters define sRNA
interactions with their targets? Our preliminary data indicate that for SgrS, the target search (where the
sRNA finds the appropriate target) is rate limiting and that this parameter is quantitatively different for each
distinct sRNA-target interaction. In Aim 1, we will use a novel super-resolution imaging platform that we
developed to further interrogate SgrS and RyhB interactions with target mRNAs and define general principles
governing sRNA-mRNA interactions. 2) How do sponge RNAs affect the regulatory efficiency of an sRNA
on many different targets? Regulation by sRNAs varies from strong effects on some targets to weak effects
on other targets. This sets up a regulatory hierarchy that we propose is central to sRNA-mediated control of
bacterial stress responses. In Aim 2, we use quantitative parameters defining sRNA regulatory efficiency and
determine how these parameters are impacted by the presence and absence of sponge RNAs, which compete
with mRNAs for binding to sRNAs. 3) What are the physiological impacts of sponge-mediated regulation
of sRNA activity and how prevalent is this level of control? Our preliminary data suggest that sponge
RNAs help tune sRNA activity so that sRNAs are only able to act on target mRNAs under the appropriate
stress conditions. Though very few have been discovered, we postulate that sponge RNAs are abundant, and
that they may be widely used to control many bacterial sRNAs. In Aim 3, we will address both of these issues
by examining the physiological consequences of sponge-mediated control of both SgrS and RyhB activity and
by conducting genome-wide analyses to identify and characterize novel targets and sponge RNAs for a variety
of bacterial sRNAs. The diverse set of techniques that we have developed and optimized will allow us to
interrogate sRNA interactions with target mRNAs on a global scale and at the level of single RNA molecules.
This will allow us to generate quantitative models for in vivo regulation by sRNAs and elucidate an extensive
sRNA regulatory network to ...

## Key facts

- **NIH application ID:** 9900794
- **Project number:** 5R01GM092830-09
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Carin K Vanderpool
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $317,205
- **Award type:** 5
- **Project period:** 2010-08-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900794

## Citation

> US National Institutes of Health, RePORTER application 9900794, Molecular Determinants of Regulatory Hierarchy for Bacterial Small RNAs (5R01GM092830-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900794. Licensed CC0.

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