The Nobel prize in physiology or medicine 2024 has been awarded to two scientists for their work on tiny RNA molecules that help cells control which proteins they produce.
Victor Ambros of the University of Massachusetts medical school, and Gary Ruvkun of Harvard medical school and Massachusetts general hospital, have been awarded the prize for the discovery of microRNA and its role in post-transcriptional gene regulation.
Announced by the Nobel assembly at Karolinska Institute, in Stockholm, Sweden, the winners will share equally a prize of 11m Swedish kronor (about £810,000).
Their work helped explain how, despite all our cells carrying the same DNA, they can produce different proteins and have different characteristics. For example, nerve cells and muscle cells are highly specialised for different functions.
“The seminal discovery of microRNA has introduced a new and unexpected mechanism of gene regulation,” said Olle Kämpe, vice-chair of the Nobel committee for physiology or medicine. “MicroRNAs are important for our understanding of embryological development, normal cell physiology, and diseases such as cancer.”
Inside the nucleus of our cells, genetic information is stored as the double-stranded molecule, DNA. To create proteins – molecules that carry out a host of functions in our cells – a section of DNA, or gene, is copied to produce a single-stranded molecule called messenger RNA (mRNA). This mRNA acts as a “go-between”, carrying the instructions for a protein to the protein-making machinery in the cells.
“The question is: what determines that only the right genes are transcribed into mRNA and then translated into the correct tissue-specific proteins at the right time?,” said Kämpe.
For many years scientists thought they had the answer in proteins called transcription factors. These bind to DNA and either activate or prevent the production of mRNA.
But as Ambros and Ruvkun revealed, that was not the full story.
Working with a type of tiny roundworm known as C.elegans the pair independently shed light on another mechanism, publishing seminal papers in the early 1990s.
Their research showed that tiny stretches of RNA, known as microRNA, could directly bind to mRNA, preventing the instructions for the corresponding protein from being “read” by protein-making machinery.
“For a long time, however, microRNA was believed to be an oddity, peculiar to C.elegans,” said Kämpe. But in the years that followed further microRNAs were discovered, with more than a thousand genes for different microRNAs known in humans today.
Later work by various teams revealed that not only can microRNA bind to mRNA to block the production of proteins, but it can cause mRNA to break down.
And there were further discoveries. “Every microRNA regulates several mRNAs and each mRNA is often regulated by many distinct microRNAs, creating a robust system for gene regulation,” said Kämpe.
Ambros and Ruvkun are no strangers to each other: the pair carried out postdoctoral research at the same time in the laboratory of Robert Horvitz, who himself shared the Nobel prize in physiology or medicine in 2002.
Prof Venki Ramakrishnan, who shared the Nobel prize in chemistry in 2009 for his work elucidating the structure of the cell’s protein-making apparatus, welcomed the news.
“This is a very well deserved and long awaited prize which shows that small RNAs can regulate which genes are expressed in different types of cells. It has opened up an entirely new field of biology and has broad implications,” he said.
But, he added, “It is a pity that David Baulcombe, whose lab discovered a similar phenomenon in plants and shared the 2008 Lasker award with Ambros and Ruvkun, was not included in the prize.”
Thomas Perlmann, secretary general of the Nobel assembly, said he was able to reach Ruvkun in the US on Monday morning, waking the scientist.
“His wife answered, and it took a long time before he came to the phone and sounded very tired, but he quite rapidly was quite excited and happy when he understood what it was all about,” Perlmann said, adding he had not yet been able to reach Ambros.
“I left a message on his mobile phone and hope he gives me a call soon,” he said.
The 2024 Nobel prize in physics will be announced on Tuesday, followed by the chemistry prize on Wednesday.
