The 2024 Nobel Prize in Medicine was awarded on Monday, October 7 to two American scientists for their discovery of microRNA - a previously unknown type of genetic switch that could lead to significant medical breakthroughs.
Despite the development of several treatments and tests using microRNAs against cancer, heart disease, viruses, and other illnesses, none have yet reached patients.
Furthermore, when Nobel laureates Victor Ambros and Gary Ruvkun unveiled their discovery decades ago, it attracted little attention, as many thought it was just “something weird about worms,” as University of Cambridge geneticist Eric Miska put it.
Messenger RNA and gene regulation
Every cell in the human body contains the same set of instructions called DNA. Some cells become brain cells, while others develop into muscles.
So, how do cells determine their specific roles? The relevant parts of the DNA instructions are highlighted through a process known as gene regulation.
Ribonucleic acid ( RNA ) typically serves as a messenger, conveying instructions from DNA to proteins - the building blocks of life that transform cells into brains or muscles.
Miska provided the example of the messenger RNA vaccines deployed against COVID-19 during the pandemic, which introduce a message with new instructions to build proteins that block viruses.
Discovery of microRNA
However, the two new Nobel winners, Ambros and Ruvkun, discovered an entirely new type of gene regulator that had previously been overlooked by science.
Rather than acting as messengers that relay information, microRNAs function as switches to turn other genes on or off.
“This was a whole new level of control that we had totally missed,” said Miska, who has worked on microRNA for two decades, including with the new Nobel laureates.
“The discovery of microRNAs brought an additional level of complexity by revealing that regions that were thought to be non-coding play a role in gene regulation,” added French researcher Benoit Ballester.
The critical role of microRNA
In the 1980s, Ambros and Ruvkun were working separately on how genes interact in one-millimeter-long roundworms called C. elegans .
When they compared their research, it led to the discovery of microRNA. Ambros published the finding in a 1993 paper.
“Nobody really paid much attention,” Miska said, explaining that most scientists at the time thought it only applied to worms.
Then, in 2000, Ruvkun published research showing that microRNA is present throughout the animal kingdom, including in humans and even some viruses.
“This was not just something weird that worms do, but in fact all animals and plants are totally dependent for development and normal function on them,” Miska said.
MicroRNA regulates hundreds of genes
It is now believed that more than a thousand genes that respond to microRNAs exist in the human body.
Many new treatments and tests using microRNA are undergoing trials, but none have been widely made available yet.
“Though there are no very clear applications available yet in microRNAs, understanding them, knowing that they exist, understanding their counter-regulatory networks, is always the first step,” said Gunilla Karlsson Hedestam, a scientist at Karolinska Institute .
Hope in the fight against cancer
MicroRNAs are particularly promising for fighting cancer because some of these switches “act as a tumor suppressor, so they put a brake on cells dividing inappropriately,” Miska explained.
Others, meanwhile, induce “cells to divide, which can lead to cancer,” he added.
Since many viruses use microRNAs, several antiviral drugs are at various stages of development, including one for hepatitis C.
However, one complicating factor has been that microRNAs can be unstable.
Scientists also hope they can be used as a test called a “biomarker,” which could reveal, for example, what type of cancer a patient might have.
According to Miska, microRNAs could also be involved in the evolution of our species. “It seems very likely that microRNAs have important roles in why the human brain is different from the brains of other primates,” he said.
Although studying human brains is challenging, Miska hopes that future research will provide more insights into how microRNAs contribute to the complex structure and functions of both human bodies and brains.
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