Nobel Prize in Physiology or Medicine awarded for discovery of microRNA gene regulation

Nobel Prize in Physiology or Medicine awarded for discovery of microRNA gene regulation

Written by Tanya Lewis

Every cell in our body contains the same set of genetic instructions, or DNA. However, only some of these genes are expressed in each cell, leading to the production of proteins that perform cell-specific functions. The 2024 Nobel Prize in Physiology or Medicine was awarded on Monday to American scientists Victor Ambrose and Gary Lubukun for their discovery of microRNAs, the molecules that carry out this important regulatory process.

This discovery opened up a new field of gene regulation and explained how only some of the many genetic instructions in DNA give rise to functional proteins in different cells. Research was initially conducted on small insects Caenorhabditis elegans, But the mechanism has since been discovered in the genes of humans and most other animals.

Mr. Ambrose conducted some of his research at Harvard University and is currently a professor of natural sciences at the University of Massachusetts Chan School of Medicine. Lubukun conducted parallel research at Massachusetts General Hospital and Harvard Medical School, where he is currently a professor of genetics.

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Ole Kampe, Vice-Chairman of the 2024 Nobel Committee for Physiology or Medicine, said at a press conference in Stockholm on Monday: “The groundbreaking discovery of microRNAs opens up new and unexpected ways of gene regulation. mechanism was introduced,” he said of the study.

Inside the cell, genes are transcribed into messenger RNA (mRNA), which is then translated into proteins. Proteins perform many important functions within every cell, whether the cell is in nerve tissue, muscle, the immune system, or elsewhere. Problems with gene function can lead to diseases such as cancer, diabetes, and autoimmune diseases.

As early as the 1960s, scientists discovered that proteins called transcription factors can bind to genes and control which parts of those genes are transcribed into mRNA. This mechanism was thought to be the main way genes are regulated. However, the reality turned out to be more complicated.

In the 1980s, Ambrose and Lubukun worked together as postdoctoral fellows in Robert Horvitz’s lab. Horwitz won the Nobel Prize in 2002 for describing the genetic regulation of cell death. nematode. Researchers studying these microorganisms had previously discovered two “mutant” genotypes of roundworms that developed differently. One of them, known as lin-4, yields larger worms, while the other, lin-14, yields smaller worms. Ambros showed that the lin-4 gene somehow negatively regulates the lin-14 gene, but it was not clear how.

Later, at Harvard University, Ambrose worked to create “clones,” or copies, of the lin-4 gene, but the result was very small RNA molecules that were too small to make proteins. . At the same time, Lubukun, then at Massachusetts General and Harvard University, was researching lin-14. He discovered that lin-4 does not block the production of lin-14 at the mRNA level, but rather prevents its translation into protein at a later stage. Ruvkun and Ambros decided to compare their findings and found that part of the lin-4 mRNA sequence matched the sequence of the lin-14 mRNA terminal region, which is not involved in protein coding. They discovered that when this lin-4 mRNA binds to lin-14 mRNA, it prevents lin-14 mRNA from producing the protein. This represents a new gene control mechanism, coordinated by small molecules called microRNAs.

Researchers initially thought this mechanism might be unique to humans. nematode. But in 2000, Ruvkun identified a second microRNA called let-7 that is present throughout humans and the animal kingdom. Scientists now know that humans have more than 1,000 different microRNA genes and that the majority of genes are controlled by microRNAs.

Disruption of these microRNA networks is thought to play a role in cancer growth and represents a potential therapy.

Ambrose and Lubukun “observed two bugs that looked a little strange, decided to try to understand why, and discovered a completely new gene regulatory mechanism,” Kampe said. “I think it’s beautiful.”

Editor’s note (10/07/24): This story is being updated.