Illuminating RNA Function with Innovative Bioluminescent Probes

RNA is a molecule that helps decode the genetic information contained in DNA. Researchers at the University of California, Irvine have found a method to tag RNA with a glowing bioluminescent molecule, which enables them to track RNA in real time as it travels.

Two human cells making RNA made visible by the bioluminescent lantern in pink (middle image). On the left, the same cells making a fluorescent protein that’s distributed evenly throughout the two cells. The right image is an overlay of the two, emphasizing that the RNA is distributed unevenly and is concentrated at specific locations. Bar on the lower right is 20 µm (1 µm is 1 millionth of a meter). Image Credit: University of California, Irvine

This technique, recently published in Nature Communications provides scientists with valuable insights into a wide range of processes, from how viruses spread to how the brain creates and stores memories.

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.”

Andrej Lupták, Professor and Study Lead Corresponding Author, University of California, Irvine

The mechanisms and timing of RNA's functions within cells remained largely unclear until recent advancements.

It turns out it is been really quite difficult to know in living cells, and especially in living organisms, when RNA is turned on and where it goes. 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.”

Andrej Lupták, Professor and Study Lead Corresponding Author, University of California, Irvine

By using the team's so-called “RNA lanterns” to tag the viral RNA, scientists can better understand how viruses compromise the body's defenses. 

Additionally, the tag might make it possible to image living brains in real time using cells that carry bioluminescent RNA. According to Jennifer Prescher, a Chemistry Professor at UC Irvine and Co-Lead Corresponding Author, RNA seems to be crucial for the brain's memory formation process.

There is a lot of interesting biology that is happening at the RNA level in neurons. 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.”

 Jennifer Prescher, Professor and Study Co-Lead Corresponding Author, Chemistry, University of California, Irvine

The team used luciferase, the same enzyme that gives insects like glowworms and fireflies their characteristic glow, to tag the RNA, because they could not figure out how to make the luciferase molecules glow bright enough for existing camera technology to detect them, scientists were previously unable to produce the results that the UC Irvine team reported.

Prescher and Lupták both attribute the research's success to UC Irvine's collaborative, interdisciplinary research culture.

We had an absolute dream team of students that were involved in this,” Prescher said, mentioning the additional co-authors Lila Halbers and Kevin Ng of the Department of Pharmaceutical Sciences and Kyle Cole of the Department of Molecular Biology and Biochemistry, as well as the third collaborator, Oswald Steward, the Reeve-Irvine Professor of Anatomy & Neurobiology and Neurobiology & Behavior.

Source:
Journal reference:

‌Halbers, L. P., et al. (2024) A modular platform for bioluminescent RNA tracking. Nature Communications. doi.org/10.1038/s41467-024-54263-5.

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