UCSD - University of California - San Diego

10/07/2026 | Press release | Distributed by Public on 10/07/2026 11:21

W. M. Keck Foundation Awards $1.3 Million to Map the Hidden 3D Architecture of Human RNA

Published Date

October 07, 2026

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The W.M. Keck Foundation has awarded $1.3 million to the University of California San Diego to support an ambitious research project to map the complex three-dimensional structures formed by RNA molecules in human cells. The project will be conducted in collaboration with researchers at the University of North Carolina at Chapel Hill.

RNA molecules play a central role in regulating how genetic information is used within cells. To perform these functions, RNA strands fold into intricate three-dimensional shapes that can form functional pockets, sites for interactions with proteins and molecular switches that help control gene expression.

Scientists can now routinely map many of RNA's simpler, secondary structures. However, the more complex folds - known as tertiary structures - remain largely uncharted in human cells because of technical and conceptual challenges.

With support from the Keck Foundation, the UC San Diego research team led by Professor of Biochemistry and Molecular Biophysics Navtej Toor and Professor Kevin Weeks from UNC Chapel Hill will work to map this previously hidden layer of RNA biology, focusing initially on structures that respond to cellular stress.

Navtej Toor

"We can now read every letter of the human transcriptome, but we still cannot see most of the shapes those letters fold into," said Toor. "RNA is not a passive string of information. It folds into intricate three-dimensional architectures and cells use those structures to decide which genes to turn on, especially under stress. Our goal is to make this hidden layer of the transcriptome visible for the first time. Once you can see a pocket, you can begin to design a molecule that fits into it."

The researchers will develop and deploy two complementary technologies. The first uses a novel chemical probe designed to identify regions of RNA with complex folds. The probe creates covalent markers at sites with high electrostatic charge density, a characteristic of unconventional RNA architecture. When paired with sequencing, the method is expected to identify sites of tertiary structure across the human transcriptome.

The second technology will allow the team to determine the three-dimensional structures of selected RNA molecules at atomic resolution using cryogenic electron microscopy, or cryo-EM. The researchers will attach target RNA molecules to an engineered RNA scaffold, enabling them to produce images at a resolution of approximately 2.5 to 3 angstroms, which is fine enough to build detailed structural models of previously unknown RNA folds.

By integrating these approaches, the team will identify stress-responsive RNA structures to then determine the precise three-dimensional architecture of the most compelling examples. The project could provide new insight into a fundamental question in biology: How do cells use three-dimensional RNA folding to regulate gene expression?

The findings are also expected to generate data that could help train the next generation of RNA structure-prediction algorithms. In addition, the technologies developed through the project could make advanced RNA structural analysis more accessible to a broader range of researchers.

"This award reflects the caliber of fundamental science happening in our department," said Christine Hrycyna, dean of the School of Physical Sciences at UC San Diego. "Professor Toor and his team are tackling a question that has remained largely inaccessible to researchers - how RNA's three-dimensional architecture governs gene expression and cellular stress responses. This generous award from the Keck Foundation will allow them to develop tools that will benefit not just their own work, but the broader RNA research community."

Ultimately, the researchers envision creating a comprehensive map of the human RNA 3D structurome, a resource that could deepen scientific understanding of the relationship between RNA structure, gene regulation and cellular responses to stress.

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