28/10/2024
Nobel Prize in Physiology or Medicine 2024
The Nobel Prize in Physiology or Medicine 2024 was awarded jointly to Victor Ambros of the University of Massachusetts Medical School and Gary Ruvkun of Harvard Medical School and Massachusetts General Hospital (MGH) for the discovery of microRNA (miRNAs) and their role in post-transcriptional gene regulation.
The reason the miRNAs are important is that a single miRNA can control many different genes. A single gene can also be regulated by multiple miRNAs. The instructions for making proteins are stored in the DNA in the nucleus of cells. RNA copies of these instructions, called messenger RNAs (mRNAs), carry this information to the protein-making factories outside the nucleus. Messenger RNAs can be many thousands of RNA letters long.
In the 1980s, Ambros and Ruvkun both worked as postdoctoral fellows in the lab of Robert Horvitz, who went on to share the 2002 Nobel Prize in Physiology or Medicine. There, they studied a roundworm, Caenorhabditis elegans, which is used as a model organism by scientists to study how cells and tissues develop into an animal. In particular, the pair carried out research on worms that carried specific mutations in their DNA that meant they developed abnormally.
The scientists had found that a gene called lin-4 seemed, somehow, to be influencing the expression of another gene, lin-14. But it wasn’t until the two scientists left to start their own labs that they discovered how this was happening. In 1993, Ambros’s group at Harvard University and Ruvkun’s group at MGH and Harvard Medical School described how lin-4 produced a short RNA molecule that didn’t code for any proteins and had a sequence that was complementary to lin-14, meaning it could bind to the latter’s miRNA.
This provided an explanation for how lin-4 could regulate lin-14, and a novel way that genes could be effectively switched on and off inside cells. But it was thought to be an oddity until 7 years later, when Ruvkun discovered another miRNA which, unlike lin-4, was found widely in organisms across the animal kingdom. Following the publication of those results in 2000, a whole field has developed to study this type of gene regulation, and tens of thousands of miRNA-encoding genes have been identified.
Researchers have since studied miRNAs’ role not only in normal development for plants and animals, but in diseases such as cancer, hearing loss and skeletal disorders. Research aiming to target miRNAs or to use them to control the expression of genes in other diseases has yet to yield any approved therapies, although numerous labs and companies are working toward this goal.
