microRNAs Discovery Wins Big: Why this Small Discovery is Such a Big Deal?

The Nobel Prize in Physiology or Medicine 2024 was given to geneticists Dr. Victor Ambros and Dr. Gary Ruvkun for their pioneering discovery of microRNAs, small RNA molecules controlling gene expression in multicellular organisms by modulating translation of messenger RNA from gene to protein.

An array of biological processes, from embryonic development to cellular functioning, have been impacted by miRNAs. Discovery of these molecules has helped to elucidate evolutionary progress – in terms of developing complex structures, such as the human brain – and has also been linked to disease progression, most notably cancer.

From Roundworms to Revolutionary Research: The Story Behind microRNA

The nobel prize winners were investigating the development of the roundworm Caenorhabditis elegans in the 1990s when they came to a preliminary conclusion that the development of these worms was determined by two particularly important genes, lin-4 and lin-14. Ambros discovered that lin-4 did not code for a protein but instead produced a short strand of RNA, now called microRNA. In doing this work on the lin-14 gene, Ruvkun filled in the last missing piece of the puzzle, and the short RNA strand, it now revealed, inhibited the translation of a protein by binding to its messenger RNA.

Ambros found that the lin-4 gene encoded a small RNA known later as microRNA that did not encode for any protein. In the meantime, Ruvkun had cloned the lin-14 gene and by collaboration, the scientists established that the sequence of the lin-4 microRNA was complementary to a sequence in the lin-14 mRNA.

This was previously considered a phenomenon only in roundworms. However, by the year 2000, Ruvkun’s laboratory had shown that miRNAs exist not only in all mammals but also in many other organisms. This discovery transformed an apparent organ-specific mechanism in worms into a universal biological process in all eukaryotes.

Revealed by Ruvkun, the identification of miRNAs in the human genome gave a breakthrough moment, when “the scientific world just went wild” with excitement. The discovery of miRNAs was one of those moments that dramatically marked the course of gene regulation studies since then. Those scientists realized that this particular component really accounted for gene control in all forms of life.

How the microRNA Rewrote Code for Gene Expression

The discovery that miRNAs are conserved across species opened up entirely new avenues of research. For decades, scientists had overlooked this entire layer of gene control because traditional methods bypassed these tiny molecules. “This was a watershed moment” in gene regulation, says RNA biologist Eric Miska of the University of Cambridge. 

Since then, hundreds of genes have been found to be modulated by miRNAs in mammals, ranging from developmental biology to cell death. This molecule gives insights into complex biological processes. In diseases such as cancer, miRNAs are oncogenes or tumor suppressors, and therefore could potentially be the target of different tools for diagnosis and treatment.

Despite the complexity of miRNA networks — in which one miRNA can affect hundreds of genes and vice versa — research in this area has exploded. Today, miRNAs are studied in neuroscience, developmental biology, and even as potential therapeutics in drug discovery.

MicroRNAs in Medicine: Opening New Doors for Diagnostics and Therapies

The discovery of miRNAs had impact far beyond gene regulation, their discovery has changed how we think about diseases, especially cancer. There is now compelling evidence that some miRNAs, including miR-21 and let-7, are deregulated in many cancers and can promote or inhibit tumor growth. Because they are stable in blood, these miRNAs are perfect candidate biomarkers for the earliest detection of cancer and could also be potential targets for new treatments.

However, designing drugs on miRNA is further challenged in the use of efficiently targeted delivery of these molecules to the tissues of concern. Still, using advancements in nanotechnology and the more advanced RNA delivery developments, treatments designed on miRNA hold much promise for disease eradication where such diseases were hitherto untreatable, including neurological disorders and a variety of cancers.

Future of microRNA research

New drugs and therapies based on miRNAs are still being developed. The 2024 Nobel Prize is a testament to how far humanity has traveled since the eyes of the world began to set its sights on the discovery of this revolutionary feature but also marks how far the future is in its genetics, with miRNAs holding the key to possibly unlocking treatments for some of mankind’s most persistent diseases.

All this lies ahead, but already we have the work of Dr. Ambros and Dr. Ruvkun reminding us how small discoveries can bring great change-and forever shift the direction of science and of medicine.

Know more about microRNA from the noble prize winning paper here.