Victor Ambros (left) and Gary Ruvkun (right) discovered microRNA, a type of molecule that helps to regulate gene activity in our cells. Credit: Steve Jennings/Getty for Breakthrough Prize
The 2024 Nobel prize in physiology or medicine has been awarded to two geneticists who discovered microRNAs, a class of tiny RNA molecules that help to control how genes are expressed in multicellular organisms.
Victor Ambros, who works at the University of Massachusetts Medical School in Worcester and Gary Ruvkun at Massachusetts General Hospital in Boston, share the prize pot of 11 million Swedish kroner (US$1.1 million), awarded by the Nobel Assembly at Karolinska Institute in Stockholm, Sweden.
The Nobel committee was unable to contact Ambros before the announcement, but managed to wake Ruvkun, who was “thrilled about the prize”, said secretary Thomas Perlmann, a molecular biologist at the Karolinska Institute.
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The two laureates, who had been post-doctoral researchers in the same group, published their first key discoveries in 19931,2. They identified the genes involved in two mutant strains of the roundworm Caenorhabditis elegans — called lin-4 and lin-14 — that did not develop properly. Ambros had found that the lin-4 gene somehow blocked the activity of the lin-14 gene, but it was not clear how. Working in their own labs, Ambros set out to map the gene responsible for lin-4, while Ruvkun initially focused on lin-14.
When Ambros identified the lin-4 gene, he was surprised to discover that it did not encode a protein, but instead an intriguingly short strand of RNA. Ruvkun’s work on lin-14 gene – which does encode a protein – helped complete the picture. The researchers found that the lin-4 ‘microRNA’ attaches to a stretch of the lin-14 messenger RNA, preventing the protein from being made through a process known as translation.
For years, the discovery was viewed as a quirk unique to roundworms, without much relevance to other organisms. That view was shattered in 2000, when Ruvkun’s team identified another C. elegans microRNA that, unlike lin-4, was shared by humans, mice and most of the animal kingdom3.
‘Beautiful’ discovery
The discovery that microRNAs were conserved across the tree of life caused the field to explode. Humans have about 1000 distinct microRNAs, more than any other organism. MicroRNAs perform a multitude of tasks in complex organisms, from embryonic development to cell physiology. MicroRNAs have been implicated in evolutionary leaps, such as humans’ bulging brains, and in the onset of cancers and other diseases.
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”It’s a completely new physiological mechanism that no one expected,” said Nobel committee member Olle Kämpe, an endocrinologist at the Karolinska Institute, at a press conference after the announcement. The work highlights the importance of curiosity in research, he added. “They were looking at two worms that looked a bit funny and decided to understand why. And then they discovered an entirely new mechanism for gene regulation. I think that’s beautiful.”
The field of ‘microRNA therapeutics’ is still in its infancy, but researchers hope to one day harness these master regulators to identify and treat diseases. “Although there are no very clear applications available yet with microRNAs, understanding them, knowing that they exist, understanding their regulatory networks is always the first step,” said Nobel committee chair Gunilla Karlsson Hedestaman, an immunologist at the Karolinska Institute. “There are quite a lot of trials ongoing, not only against cancer but also in other diseases, like cardiovascular and kidney diseases.”
This is a breaking news story that will be updated throughout the day.
Additional reporting by Helena Kudiabor.
