# Discovery and Function of Higher-Order RNA Structure

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $619,618

## Abstract

SUMMARY
RNA functions as the central conduit of information exchange in all cells. RNA molecules encode this
information in both their primary sequences and in complex structures that form when RNA folds back
on itself. A consistent theme from our MIRA-supported work to date is that biological function mediated
by RNA structure is ubiquitous in both eubacterial and eukaryotic organisms. The broad and
fundamental importance of RNA structure is clear, but there remains a profound knowledge gap: We
generally have only rudimentary understanding of RNA structure across vast regions of most
messenger and non-coding RNAs. We need to move beyond modeling RNA structure to directly
detecting through-space structural communication and interactions in cells. Our lab takes a near-unique
approach, simultaneously focusing on experimental simplicity and directness and on extensive
validation in model systems. In essentially every instance where we have applied rigorous and
quantitative technologies to study RNA structure-function interrelationships, new insights regarding
biological regulatory mechanisms have emerged. We have also shown that RNA elements with higher-
order structures are more likely to contain high-information-content clefts and pockets that bind small
molecules, broadly informing a vigorous field of RNA-targeted drug discovery. This work is designed to
have sustained long-term impact by pursuing three overarching opportunities. First, the project focuses
on development of decisive, concise, and broadly implementable technologies for discovering and
assessing higher-order structure in RNA. Second, this project applies these direct and experimentally
concise methods to challenges of broad importance, from identification of structures essential for
replication of pathogenic viruses to understanding how RNA conformational ensembles govern
transcriptional gene regulation and pre-mRNA splicing. Third, understanding the propensity of RNA to
form higher-order structures – and often clefts and pockets – opens up the possibility of targeting these
motifs with small molecules, an opportunity we will exploit with the long-term goal of inventing facile and
straightforward strategies for creating RNA-targeted therapeutics.

## Key facts

- **NIH application ID:** 10330618
- **Project number:** 2R35GM122532-06
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Kevin M Weeks
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $619,618
- **Award type:** 2
- **Project period:** 2017-06-09 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330618

## Citation

> US National Institutes of Health, RePORTER application 10330618, Discovery and Function of Higher-Order RNA Structure (2R35GM122532-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10330618. Licensed CC0.

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