# Interplay of RNA Structural Motifs with Base Modifications

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $337,875

## Abstract

PROJECT SUMMARY
Viral RNA, like the human transcriptome, is punctuated by infrequent but critical base modifications and non-
Watson-Crick motifs. Many knowledge gaps exist in understanding where, when and why certain
modifications such as pseudouridine (Ψ) and N6-methyl-adenosine (m6A) are enzymatically written onto
mRNA. Similarly, guanosine-rich regions of viral RNA and the human transcriptome that may potentially fold
to G-quadruplex motifs are conserved in regulatory regions controlling translation and viral replication for
reasons that remain unclear. This research project hypothesizes that secondary structural motifs such as
stem-loop structures and G-quadruplexes constitute the recognition sites for RNA modification. Additionally,
these sites are hotspots for oxidative modification (8-oxo-7,8-dihydroguanosine, rOG) such as occurs during
oxidative stress generated by viral infections. Thus, the project will examine the interplay of base modification
(pseudouridinylation, guanosine oxidation and adenosine methylation) with secondary structural motifs in
RNA. New innovative chemical biology tools will be developed to sequence long mRNA strands for folded
structures by examining the ability of protein nanopores to thread and translocate folded or unfolded RNA.
Similarly, base modifications will be identified using specific chemistries to amplify signals from base
modification. The specific aims are to (1) investigate the sequence vs. structural motif of pseudouridine
locations in ZIKV RNA, (2) sequence for rOG and correlate sites with secondary structure vs. solvent
exposure, and (3) correlate G4 folds of ZIKV RNA with m6A. The human health relevance of this research is
to provide foundational science for understanding the molecular choreography of mRNA, both human and
viral, in order to advance health strategies combatting viral infection, cancer, and age-related disorders.

## Key facts

- **NIH application ID:** 10246857
- **Project number:** 5R01GM093099-10
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Cynthia J Burrows
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $337,875
- **Award type:** 5
- **Project period:** 2011-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246857

## Citation

> US National Institutes of Health, RePORTER application 10246857, Interplay of RNA Structural Motifs with Base Modifications (5R01GM093099-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10246857. Licensed CC0.

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