# Dynamics of co-transcriptional riboswitch folding through single-molecule microscopy

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $65,610

## Abstract

Project Abstract and Summary:
RNA elements known as riboswitches are critical for proper genome expression and maintenance in many
prokaryotes. Riboswitches are generally found upstream, in the 5’ untranslated region of an mRNA, and fold
co-transcriptionally to structurally impede mRNA transcription and/or translation. In the presence of specific
RNA binding ligands, riboswitches undergo alterations in secondary structure that either: 1) disallow translation
initiation, or 2) result in altered transcription termination. Riboswitches are rarely found in eukaryotes, and thus
present a novel vulnerability that can be targeted for anti-bacterial therapies. It has been clearly demonstrated
in the literature that nascent RNA structure influences transcriptional activity of the transcribing polymerase in
bulk assays, but little work has been done on how the transcribing polymerase itself influences nascent RNA
structure in return. Further, RNA structure has been shown to impact active site conformations of the
polymerase, but never in the context of the riboswitch. In this study we will comprehensively examine the
mechanisms by which riboswitches influence the transcribing RNAP, and vice versa, using cutting
edge single-molecule techniques.
In addition to the novel science proposed in this application, this fellowship will further enhance my training,
and strengthen me as an independent scientist. I will participate in seminars, workshops, mentoring and teach
opportunities, as well as professional development and networking opportunities afforded to me by the diverse
collection of programs offered at the University of Michigan (including programs organized by: the College of
Literature, Sciences, and the Arts, the Life Sciences Institute, the Department of Chemistry, the Center for
RNA Biomedicine, the Michigan Life Sciences Fellowship, the Office of Graduate Student and Postdoctoral
Affairs, and the University of Michigan Postdoctoral Association). Further, Dr. Nils Walter has already
demonstrated excellent mentorship skills, and his lab is comprised of a large, diverse group of postdoctoral
fellows and graduate students with whom I can find support and guidance. Our lab also includes a large
number of talented undergraduates which will provide me with many opportunities for collaborating with
younger mentees. Overall, the research planned in this proposal, and the support granted to me by this
program, will enrich both me and the field of riboswitch RNA biology.

## Key facts

- **NIH application ID:** 10140865
- **Project number:** 1F32GM140547-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Catherine Scull
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,610
- **Award type:** 1
- **Project period:** 2021-01-27 → 2024-01-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140865

## Citation

> US National Institutes of Health, RePORTER application 10140865, Dynamics of co-transcriptional riboswitch folding through single-molecule microscopy (1F32GM140547-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10140865. Licensed CC0.

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