The 2024 Nobel Prize in Physiology or Medicine was awarded on October 7th to Victor Ambros and Gary Ruvkun for their discovery of microRNAs (miRNAs). This ground-breaking finding transformed our understanding of how gene activity is controlled. I am the author of a new book on the topic: ‘Fine-Tuning Life: A guide to microRNAs, your genome’s master regulators’. So, let me guide you through what you need to know. What exactly are miRNAs, and why is the Nobel Prize recognition so deserved?
MicroRNAs (miRNAs) are a type of gene, but not a gene in the traditional sense. When we talk about ‘genes’ most people are referring to protein-coding genes – the sequences of DNA that are the instructions to build a protein, such as haemoglobin or insulin. Instead, miRNA genes play a regulatory role, producing short RNAs that control how and when proteins are made in our cells. So, miRNAs are our genome’s fine-tuning system.
Imagine miRNAs as molecular Velcro, sticking to the mRNAs that are to be translated into protein. miRNAs block these messages from reaching the protein-production machinery inside our cells, known as the ribosome which an earlier Nobel prize went to. Their effect is a bit like tying a knot in a shoelace to stop it from being threaded through. By controlling this process, miRNAs ensure that proteins are made at the right time and in the right amounts.
By regulating gene activity, miRNA help our cells function properly. miRNA genes are always busy, working inside cells from the moment of fertilisation throughout every moment of our lives until we die. This is especially important in the brain, which contains the highest levels of active miRNAs.
‘Master controllers’ of gene expression
miRNAs are sometimes referred to as ‘master controllers’ or ‘conductors of the molecular orchestra’ because each miRNA can stick to dozens of these protein-coding mRNAs. That makes them very powerful or influential, giving them oversight of virtually every process inside our cells.
Regular gene activity can be noisy and unstable – miRNAs provide a stabilising effect through negative feedback to keep things in balance. In a way, miRNAs are like a cooling system for our genome. But their actions also create other important benefits – miRNAs create a richer repertoire of gene activity patterns than is possible with ‘just’ protein-coding genes. This enables organisms to be far more complex. Consider that while humans and the worm C. elegans (the organism that Ambros and Ruvkun were studying when they discovered miRNAs) have a similar number of protein-coding genes, the human genome contains 25 times more miRNA genes. More miRNA means more cellular complexity – there are primate and human-specific miRNA genes, most of which are active in the brain.
Applications of the discovery
The discovery of miRNAs has paved the way for significant advancements in medicine. Testing for levels of miRNAs has become a way to check for cancers, and scientists are exploring their potential as therapeutic targets in various human diseases.
Fine-Tuning Life
I began my book by introducing genes and proteins and then covering the original 1993 discoveries by Ambros and Ruvkun. The next chapter covers the explosion of interest that followed when miRNA genes were discovered in humans. I trace their evolution back to the earliest moments in the history of life on Earth, and looks at how miRNAs helped complex life evolve. After that, I describe how miRNAs are produced in cells and how they perform their jobs. The book takes a special look at development and the role of miRNAs in the brain. In later chapters, the book focuses on how miRNAs impact on human health, in particular conditions affecting the brain. The discoveries on miRNA have important applications in medicine and biotechnology and I include some of my laboratory’s research. At FutureNeuro (www.futureneurocentre.ie), the Research Ireland Centre for Translational Brain Science, miRNAs are a cornerstone of our research. One exciting project involves developing a miRNA-based drug to treat epilepsy, a testament to the far-reaching impact of this Nobel prize-winning discovery. Finally, what is next? My book finishes with questions researchers are asking now, and hope to answer in the future..
Title: Fine-Tuning Life: A guide to microRNAs, your genome’s master regulators
ISBN: 9781009466424
Author: David C. Henshall
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