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U.S. Scientists Win Nobel Prize in Medicine for Discovery of mRNA
  • Posted October 7, 2024

U.S. Scientists Win Nobel Prize in Medicine for Discovery of mRNA

A pair of American scientists have won the 2024 Nobel Prize in medicine for their discovery of microRNA, tiny genetic molecules that play a crucial role in how genes shape the body.

The research of Victor Ambros and Gary Ruvkun “revealed a new dimension to gene regulation, essential for all complex life forms,” including human beings, the Nobel committee wrote in a Monday news release announcing the honor.

Gene regulation by microRNA has been at work for hundreds of millions of years, enabling the evolution of increasingly complex organisms, the Nobel committee said.

But until Ambros and Ruvkin’s discovery, microRNA remained a hidden influence.

A better understanding of microRNA’s role in genetics could lead to better treatments for diseases like cancer, diabetes and autoimmune disorders, the Nobel committee said.

“We know from genetic research that cells and tissues do not develop normally without microRNAs,” the committee wrote. “Abnormal regulation by microRNA can contribute to cancer, and mutations in genes coding for microRNAs have been found in humans, causing conditions such as congenital hearing loss, eye and skeletal disorders.”

Ambros is a professor of natural science at the University of Massachusetts Medical School, and Ruvkin is a professor of genetics at Harvard Medical School.

Every cell in a person’s or animal’s body contains their entire genetic code, meaning that each cell carries an instruction manual for how to create any cell in a body.

However, the body contains very different cell types like muscle, skin and nerve cells. How these specialized cells choose what part of the genetic code to follow in their development?

The answer lies in gene regulation, the process by which each cell selects only the instructions relevant to it. “This ensures that only the correct set of genes is active in each cell type,” the Nobel committee explained.

At the time of Ambrose and Ruvkin’s discovery, scientists had thought they fully understood the process of gene regulation because it had been shown that specialized proteins called transcription factors could control the flow of genetic information.

“Since then, thousands of transcription factors have been identified, and for a long time it was believed that the main principles of gene regulation had been solved,” the committee wrote. “However, in 1993, this year’s Nobel laureates published unexpected findings describing a new level of gene regulation, which turned out to be highly significant and conserved throughout evolution.”

Their initial discovery centered around a “relatively unassuming 1-millimeter-long roundworm” called C. elegans, the committee wrote. Even though it’s tiny, the roundworm possesses many specialized cell types like nerve and muscle cells also found in larger and more complex animals.

In the late 1980s, Ambros and Ruvkin started researching C. elegans as postdoctoral fellows in the MIT lab of previous Nobel laureate Robert Horvitz. They continued their focus on the roundworm after going their separate academic ways.

Focusing on a mutation in the roundworm, Ambros discovered a tiny RNA molecule that appeared to block a specific gene called lin-14 but didn’t seem to serve any other purpose.

In his own research, Ruvkin cloned the lin-14 gene from the roundworm and found that it was being inhibited by something outside the process of gene regulation as it was understood at the time.

Comparing results, the researchers found that the microRNA molecule was turning off the lin-14 gene by binding to its messenger RNA, a substance produced by a gene to guide cell production.

“A new principle of gene regulation, mediated by a previously unknown type of RNA, microRNA, had been discovered,” the Nobel committee wrote.

The pair published their results in 1993, and “were initially met with almost deafening silence from the scientific community,” the committee said. 

Critics said the unusual mechanism of gene regulation could be a quirk of C. elegans, and if so would be likely irrelevant to more complex animals like humans.

But in 2000, Ruvkin’s research group discovered another microRNA encoded by a gene that is present throughout the animal kingdom, showing that the process does play an ongoing role in gene regulation.

“Over the following years, hundreds of different microRNAs were identified,” the Nobel committee wrote. “Today, we know that there are more than a thousand genes for different microRNAs in humans, and that gene regulation by microRNA is universal among multicellular organisms.”

Subsequent research also has found that a single microRNA can regulate many different genes, and a single gene can be regulated by multiple microRNAs, the committee said.

More information

Ohio State University has more on microRNA.

SOURCE: The Nobel Foundation, news release, Oct. 7, 2024

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