The Swedish Academy announced that Victor Ambros and Gay Ruvkun have been awarded the 2024 Nobel Prize in Medicine for research that led to “the discovery of microRNA and its role in post-transcriptional gene regulation.”
“Their revolutionary discovery in the small worm C. elegans revealed a completely new principle of genetic regulationwhich has been shown to be essential for multicellular organisms, including humans. “MicroRNAs prove to be of fundamental importance for the development and functioning of organisms,” said the Royal Swedish Academy of Sciences, which is awarding the first of this year’s Nobel Prize laureates on Monday. Europe Press.
Victor Ambros, born in 1953 in Hanover, and Gary Ruvkun in Gary Ruvkun, born in Berkeley, in 1952, both Americans, were interested in how different types of cells develop. They discovered microRNAs, a new class of tiny RNA molecules that play a crucial role in gene regulation.
His revolutionary discovery revealed a completely new principle of gene regulation that proved essential for multicellular organismsincluding humans. We now know that the human genome encodes more than a thousand microRNAs. Their surprising discovery revealed a whole new dimension of genetic regulation. MicroRNAs appear to be of fundamental importance for the development and function of organisms.
In the late 1980s, Ambros and Ruvkun were postdoctoral fellows in the laboratory of 2002 Nobel Prize winner Robert Horvitz, alongside Sydney Brenner and John Sulston. In Horvitz’s lab, they studied a relatively modest 1 mm long roundworm, C. elegans’. Despite its small size, ‘C. elegans has many specialized cell types, such as nerve and muscle cells, that are also found in larger, more complex animals, making it a useful model for studying tissue development and maturation in multicellular organisms.
Ambros and Ruvkun were interested in genes that control the timing of activation of different genetic programs, ensuring that different cell types develop at the right time. They studied two mutant strains of worms, lin-4 and lin-14, which had defects in the timing of activation of genetic programs during development. The winners wanted to identify mutated genes and understand their function. Ambros previously showed that the lin-4 gene appears to be a negative regulator of the lin-14 gene. However, it was unclear how lin-14 gene activity was blocked. Ambros and Ruvkun were intrigued by these mutants and their possible relationship and set out to solve these mysteries.
Following his postdoctoral research, Victor Ambros analyzed the lin-4 mutant in his new laboratory at Harvard University. Methodical mapping enabled the cloning of the gene and led to an unexpected discovery. The lin-4 gene produced an unusually short RNA molecule lacking a code for protein production. These surprising results suggest that this small RNA lin-4 was responsible for the inhibition of lin-14.
At the same time, Gary Ruvkun was studying the regulation of the lin-14 gene in his newly established laboratory at Massachusetts General Hospital and Harvard Medical School. Contrary to how gene regulation was then known to work, Ruvkun showed that it is not the production of mRNA from lin-14 that is inhibited by lin-4. Regulation appears to occur at a later stage in the gene expression process, via cessation of protein production.
The experiments also revealed a segment in lin-14 mRNA that was required for its inhibition by lin-4. The two winners compared their results, resulting in a revolutionary discovery. The short lin-4 sequence corresponded to complementary sequences in the critical segment of lin-14 mRNA. Ambros and Ruvkun performed further experiments that showed that microRNA lin-4 inactivates lin-14 by binding to complementary sequences of its mRNA, thereby blocking production of the lin-14 protein.
This discovery was a new principle of genetic regulation, mediated by a previously unknown type of RNA, microRNA. The results were published in 1993 in two articles in the journal “Cell”. Although the results are interesting, the unusual mechanism of gene regulation has been considered a peculiarity of ‘C. elegans’, probably unrelated to humans and other more complex animals.
A change in the year 2000
This perception changed in 2000 when Ruvkun’s research group published their discovery of another microRNA, encoded by the let-7 gene. Unlike lin-4, the let-7 gene was highly conserved and present throughout the animal kingdom. The paper generated great interest, and over the next few years hundreds of different microRNAs were identified.
“Today, we know that there are more than a thousand genes for different microRNAs in humans and that gene regulation by microRNAs is universal among multicellular organisms. In addition to mapping new microRNAs, Experiments carried out by several research groups have elucidated the mechanisms of production and transport of microRNAs towards complementary target sequences in regulated mRNAs.
