This year’s Nobel Prize in Physiology or Medicine has been awarded to two American scientists, Victor Ambros and Gary Ruvkun, for their groundbreaking discovery of microRNA (miRNA), tiny RNA molecules that play a crucial role in regulating gene activity. Their research has unveiled an essential mechanism that controls how our cells decide which genes to express and when. And this discovery has revolutionized our understanding of genetic regulation.

MicroRNA

For decades, scientists have sought to answer how our cells, all containing the same DNA, can give rise to such vastly different cell types. Why do nerve cells, muscle cells, and liver cells look and function so differently despite having identical genetic information? Ambros and Ruvkun’s work on microRNA provided a key piece of that puzzle.

The two researchers were curious to figure out how different cell types develop. DNA serves as the blueprint, and every cell carries a copy of this. However, the type of cell that forms depends on which parts of the DNA are activated (or “expressed”). This process is called gene regulation, and this is what ensures that cells only use the instructions relevant to them.

To create proteins, a section of DNA (the double-stranded molecule) is copied to produce a single-stranded molecule called messenger RNA (mRNA — not to be confused with miRNA). As the name implies, this molecule has the role of messenger. It carries instructions for the protein-making structures in the cells.

In the 1960s, we discovered that some proteins (called transcription factors) can bind to parts of the DNA. Thus, they controlled the instructions that cells receive by determining which mRNAs are produced. This was a key part of cell diversification, but as the two recent laureates showed, it’s not the only part — microRNAs also play a role.

MicroRNAs are small but powerful regulators of gene expression. They work by binding to complementary sequences in their target mRNAs, blocking the production of proteins or triggering the destruction of the mRNA altogether. This elegant mechanism of gene regulation allows cells to fine-tune protein production based on their needs and environmental conditions.

A second layer of control

Ambros and Ruvkun’s discovery revealed that microRNAs can bind directly to mRNAs and prevent them from being translated into proteins, offering a second layer of control that operates after inscription. This newfound mechanism has profound implications for our understanding of how cells develop, function, and adapt.

In two groundbreaking 1993 studies, the two researchers demonstrated this in a worm called C. elegans, a common model organism. Over the next few years, the researchers continued working on this. Then, in 2000, Ruvkun’s group showed that many species, including humans, have microRNA and use it similarly to C. elegans. Since then, over a thousand distinct microRNAs have been discovered in humans.

“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.”

This was groundbreaking because the initial reactions from the scientific community were mixed. Many scientists assumed that microRNAs must be a peculiarity of C. elegans. The fact that they are so common cemented Ambros’ and Ruvkun’s status as true pioneers of the field.

A Newly Formed Field

Today, the field of microRNA research continues to expand. In addition to their role in disease, microRNAs are proving to be vital players in immune function, tissue repair, and even brain development. Ambros and Ruvkun’s work has opened up entirely new research areas, leading to discoveries that extend far beyond the original scope of their studies.

The discovery of microRNA regulation has significant implications for human health. When the gene-regulation system involving microRNAs goes awry, it can lead to serious diseases. Among these are cancer, diabetes, and autoimmune disorders. For example, certain cancers arise when microRNAs that should suppress oncogenes (genes that can cause cancer) fail to function properly, allowing uncontrolled cell growth.

The recognition of the new Nobel laureates was widely hailed by the scientific community.

In addition to the glory, the two researchers will also share a prize fund worth 11m Swedish kronor (£810,000).