# Role of structural dynamics in RNA regulation

> **NIH NIH R35** · BAYLOR COLLEGE OF MEDICINE · 2022 · $400,000

## Abstract

Project Summary
Messenger RNAs (mRNAs) encode complex regulatory instructions in their 3' untranslated
regions (3'UTRs) that prescribe context-dependent control of translation and decay. Disruption
of mRNA post-transcriptional regulation by mutational lesions or shortening of 3'UTRs has been
linked to diverse human diseases. RNA molecules fold back on themselves into base-paired
secondary structures and occasionally higher-order tertiary structures, and sequence-encoded
structures are hypothesized to play key roles in directing 3'UTR regulation. For example, RNA
structures can provide specific binding sites for RNA binding proteins and may tune the
accessibility of microRNA target sites. RNA structures may also function as molecular switches,
with protein or microRNA binding triggering specific 3'UTR structural changes that alter the
activity of distal regulatory sites. However, little remains known about 3'UTR structures and their
role in post-transcriptional regulation. Existing data indicate that 3'UTRs have heterogenous and
dynamic structures, which makes them challenging to study by traditional chemical probing or
biophysical methods. My research group has recently developed a new single-molecule
chemical probing technology (DANCE-MaP) that makes it possible to accurately define RNA
structural ensembles consisting of 2-3 coexisting states in living cells. We will pursue two areas
of research that exploit and build on the DANCE-MaP technology: (1) We will apply DANCE-
MaP to define 3'UTR folding landscapes and mechanisms of combinatorial regulation by RNA
binding proteins and microRNAs. (2) We will develop next-generation technologies that can
resolve structurally heterogenous RNAs with greater resolution and provide model-free, physical
interpretation of chemical probing data. This work will provide an improved understanding of
mRNA regulatory mechanisms, helping advance efforts to therapeutically target 3'UTRs to
modulate gene expression, and contribute new structure determination technologies that will be
of broad utility to the RNA biology field.

## Key facts

- **NIH application ID:** 10499994
- **Project number:** 1R35GM147010-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Anthony McDowell Mustoe
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499994

## Citation

> US National Institutes of Health, RePORTER application 10499994, Role of structural dynamics in RNA regulation (1R35GM147010-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10499994. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*