Victor Ambros and Gary Ruvkun are announced as the winners of the 2024 Nobel prize in physiology or medicine
Jonathan Nackstrand AFP via Getty Images
The 2024 Nobel prize in physiology or medicine has been awarded to Victor Ambros and Gary Ruvkun for the discovery of tiny pieces of RNA, called microRNAs, that play a key role in regulating gene activity in animals and plants.
The reason they are important is that a single microRNA can control many different genes. A single gene can also be regulated by multiple microRNAs.
“The seminal discovery of microRNAs has introduced a new and unexpected mechanism of gene regulation,” said Olle Kämpe, the vice-chair of the Nobel committee for physiology and medicine. “These are important for our understanding of embryological development, normal physiology and diseases such as cancer.”
Ambros and Ruvkun made the discovery while studying mutant strains of a nematode worm called Caenorhabditis elegans. Their work began in the 1980s while at the same lab. Ambros then moved to Harvard University and Ruvkun to Massachusetts General Hospital, where they continued studying the mutant strains.
The instructions for making proteins are stored in the DNA in the nucleus of cells. RNA copies of these instructions, called messenger RNAs, carry this information to the protein-making factories outside the nucleus. Messenger RNAs, or mRNAs, can be many thousands of RNA letters long.
One way to control gene activity is to stop mRNAs being made in the first place. Another is to stop mRNAs reaching the protein-making factories. In both cases, the result is to prevent the production of the protein encoded by the gene – or, as biologists say, to switch off the gene.
MicroRNAs work in the second way. They are tiny pieces of RNA, around 20 base pairs long, whose sequence is complementary to part of one or more mRNAs. When a microRNA binds to its complementary sequence on an mRNA, it typically leads to the breakdown of that mRNA before any protein can be made.
MicroRNAs usually act within a cell, but are sometimes released by cells to control activity elsewhere in a body. In some cases, organisms even release microRNAs to control other organisms. This is usually done by disease-causing organisms, but one symbiotic fungi was recently discovered to release microRNAs to help it colonise tree roots.
Many groups are working on treatments based on microRNAs, but so far none have yet been approved. The presence or absence of microRNAs can also help diagnose certain medical conditions.
Ambros and Ruvkun were the first to discover a microRNA, in work done in the 1990s. However, the one they discovered, called lin-4, controls only one gene, and the way it works was assumed to be specific to nematode worms. Because of this, their discovery received little attention.
In 2000, Ruvkun reported the discovery of another microRNA, called let-7. This controls five genes, and turned out to be widespread in animals. That led to huge interest in microRNAs, and many thousands have now been discovered in a wide array of organisms.
Thomas Perlmann, the secretary-general of the Nobel assembly, said he hadn’t yet contacted Ambros, but had spoken to Ruvkun and his wife. “They were thrilled about the prize and coming to Stockholm,” said Perlmann.
The 2023 Nobel prize in physiology or medicine was awarded to Katalin Karikó and Drew Weissman for working out how to tweak mRNA to avoid its destruction by the immune system, which was key to the development of mRNA vaccines, including the covid-19 ones.
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