Stockholm, Sweden (DT) —This year’s Nobel Prize honors two scientists Nobel Prize in medicine honors Victor Ambros and Gary Ruvkun for their discovery of microRNA for their discovery of a fundamental principle governing how gene activity is regulated.
The information stored within our chromosomes can be likened to an instruction manual for all cells in our body. Every cell contains the same chromosomes, so every cell contains exactly the same set of genes and exactly the same set of instructions. Yet, different cell types, such as muscle and nerve cells, have very distinct characteristics.
What is the Nobel Prize for?
RNA is best known for carrying instructions for how to make proteins from DNA in the nucleus of the cell to tiny cellular factories that actually build the proteins. MicroRNA does not make proteins, but helps to control what cells are doing, including switching on and off critical genes that make proteins.
How do these differences arise? The answer lies in gene regulation, which allows each cell to select only the relevant instructions. This ensures that only the correct set of genes is active in each cell type.
Victor Ambros and Gary Ruvkun were interested in how different cell types develop. They discovered microRNA, a new class of tiny RNA molecules that play a crucial role in gene regulation.
Their groundbreaking discovery revealed a completely new principle of gene regulation that turned out to be essential for multicellular organisms, including humans. It is now known that the human genome codes for over one thousand microRNAs. Their surprising discovery revealed an entirely new dimension to gene regulation. MicroRNAs are proving to be fundamentally important for how organisms develop and function.
Essential regulation
This year’s Nobel Prize focuses on the discovery of a vital regulatory mechanism used in cells to control gene activity. Genetic information flows from DNA to messenger RNA (mRNA), via a process called transcription, and then on to the cellular machinery for protein production. There, mRNAs are translated so that proteins are made according to the genetic instructions stored in DNA. Since the mid-20th century, several of the most fundamental scientific discoveries have explained how these processes work
Our organs and tissues consist of many different cell types, all with identical genetic information stored in their DNA. However, these different cells express unique sets of proteins. How is this possible? The answer lies in the precise regulation of gene activity so that only the correct set of genes is active in each specific cell type.
This enables, for example, muscle cells, intestinal cells, and different types of nerve cells to perform their specialized functions. In addition, gene activity must be continually fine-tuned to adapt cellular functions to changing conditions in our bodies and environment. If gene regulation goes awry, it can lead to serious diseases such as cancer, diabetes, or autoimmunity. Therefore, understanding the regulation of gene activity has been an important goal for many decades.
In the 1960s, it was shown that specialized proteins, known as transcription factors, can bind to specific regions in DNA and control the flow of genetic information by determining which mRNAs are produced. Since then, thousands of transcription factors have been identified, and for a long time it was believed that the main principles of gene regulation had been solved. However, in 1993, this year’s Nobel laureates published unexpected findings describing a new level of gene regulation, which turned out to be highly significant and conserved throughout evolution.
Research on a small worm leads to a big breakthrough
In the late 1980s, Victor Ambros and Gary Ruvkun were postdoctoral fellows in the laboratory of Robert Horvitz, who was awarded the Nobel Prize in 2002, alongside Sydney Brenner and John Sulston. In Horvitz’s laboratory, they studied a relatively unassuming 1 mm long roundworm, C. elegans. Despite its small size, C. elegans possesses many specialized cell types such as nerve and muscle cells also found in larger, more complex animals, making it a useful model for investigating how tissues develop and mature in multicellular organisms. Ambros and Ruvkun were interested in genes that control the timing of activation of different genetic programs, ensuring that various cell types develop at the right time.
They studied two mutant strains of worms, lin-4 and lin-14, that displayed defects in the timing of activation of genetic programs during development. The laureates wanted to identify the mutated genes and understand their function. Ambros had previously shown that the lin-4 gene appeared to be a negative regulator of the lin-14 gene. However, how the lin-14 activity was blocked was unknown. Ambros and Ruvkun were intrigued by these mutants and their potential relationship and set out to resolve these mysteries.
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