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UC Irvine researchers develop bioluminescent RNA for real-time tracking

By Heather Hall | January 9, 2025

Bison Gate UCI monument sign
photo: Steve Zylius/UCI

Scientists at the University of California, Irvine, have developed a method for tagging RNA with a bioluminescent molecule, which enables real-time tracking of RNA as it moves throughout the body. This research, published in Nature Communications, could provide new insights into cellular processes, viral propagation, and memory formation in the brain.

RNA is critical in cellular function as the intermediary translating DNA’s genetic instructions. Little is known about RNA’s behavior within living cells despite its importance.

“The first step in saying something’s going to happen in a cell – the cell is going to grow, adapt, change or anything like that – underlying all of that is RNA,” said Andrej Lupták, a professor of pharmaceutical sciences at UC Irvine and one of the lead corresponding authors of the study.

Until now, little was known about how and when RNA does what it does inside cells. “It turns out it’s been really quite difficult to know in living cells, especially in living organisms, when RNA is turned on and where it goes,” said Lupták. “If you wanted to study the first 30 seconds or the first minute – nobody knows. But we provide a tool. You can now visualize it.”

The team created the “RNA lanterns” by tagging RNA with luciferase, the enzyme responsible for fireflies’ glow. This breakthrough overcomes a longstanding challenge: previous attempts to use luciferase struggled with brightness levels insufficient for detection. The UC Irvine team resolved this, allowing researchers to track RNA dynamics in previously unattainable ways.

Applications in virus research and neuroscience

The method has immediate implications for understanding viral mechanisms. Viruses replicate by injecting RNA into host cells. Tagging viral RNA with the bioluminescent molecule could help scientists observe how viruses infiltrate cells and spread.

The tag could also allow for real-time imaging of living brains with cells carrying bioluminescent RNA. Jennifer Prescher, co-lead corresponding author and UC Irvine professor of chemistry, explains that RNA appears to play a key role in the formation of memories in the brain.

“There’s a lot of interesting biology that’s happening at the RNA level in neurons,” said Prescher. “And being able to see early events and the transport of RNA from the cell body out to neural synapses where connections are being made to other neurons – that directly correlates with memory formation. If you have a way to watch that in real time, that could tell you something fundamental about the brain and memory, which has been a holy grail in science for a long time.”

A collaborative achievement

The study’s success stemmed from UC Irvine’s collaborative research environment. The team included graduate students and faculty from multiple pharmaceutical sciences, molecular biology, and neurobiology departments. The research was funded by a W. M. Keck Foundation grant awarded to Lupták, Prescher, and Oswald Steward, a co-collaborator and professor of neurobiology.

This new tool could advance RNA research. It offers a window into previously obscured cellular mechanisms and has wide-ranging applications in biology and medicine.

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