The Nobel Prize in Medicine 2024 was awarded to Victor Ambros and Gary Ruvkun for their work on the discovery of microRNA, a class of RNA molecules (ribonucleic acid) which regulate gene expression.
Several funded research projects in the field of RNA are currently underway at Instituto Superior Técnico. One of these projects aims to identify and characterise the biological functions of non-coding RNAs from a group of bacteria that cause respiratory infections in patients with cystic fibrosis and use this knowledge to establish new therapeutic approaches. Other projects focusing on RNA aim to optimise techniques for producing and purifying messenger RNA for use in vaccines or develop new RNA molecules with fungicidal activity.
Jorge Leitão, a professor at Instituto Superior Técnico and a researcher at the Institute for Bioengineering and Biosciences (iBB), clarifies some of the questions about the work awarded this year by the Karolinska Institute.
What is microRNA and what cellular mechanisms it involves?
The genetic information of an organism is stored in the DNA. The information in DNA is transferred to a messenger RNA (mRNA) molecule by way of a process called transcription, which will then be translated into proteins. This transcription process gives rise to messenger RNAs and also to non-coding RNA molecules, which, for a long time, we didn’t know what they were for.
It is now known that microRNAs belong to a group of RNAs that are transcribed from DNA and do not encode proteins, but play a fundamental role in regulating gene expression. In a normal cell, not all genes are translated at the same time and changes in the environment mean that certain essential proteins are no longer needed. MicroRNAs are a rapid way of regulating gene expression in the face of changes experienced by organisms, allowing them to quickly adapt their cellular functions to new conditions.
MicroRNA and messenger RNA (mRNA) are therefore different concepts. How do they interact?
MicroRNAs are capable of interacting with messenger RNA molecules, by binding to the latter in a complementary sequence. This process involves protein complexes that help with this binding. When binding occurs, the messenger RNA is inactivated, meaning that it cannot be translated into new proteins. MicroRNAs therefore play their role in regulating gene expression at the post-transcriptional level [i.e. after the DNA transcription process]. MicroRNAs thus play a fundamental role in the physiology of cells. Their more practical importance stems from the fact that microRNAs have been associated with various diseases in humans, such as cancer and some degenerative diseases. Understanding the mechanisms of action of microRNAs will allow to design new molecules and strategies to combat these diseases.
What scientific breakthroughs have resulted from Ambros and Ruvkun’s work? What benefits could they bring to the future of medicine?
Knowledge of microRNAs has revolutionised our understanding of the mechanisms regulating gene expression. Until then, it was thought that gene expression depended solely on its transcription into mRNA, which would subsequently be translated into protein. However, the discovery of microRNAs made it possible to realise that, in addition, mRNAs themselves are subject to the action of microRNAs, allowing cells to quickly and very finely adjust the levels of certain proteins, always with a view to saving the cell’s resources.
Ambros and Ruvkun’s work also pioneered the discovery that this regulation mechanism is more general, extending to practically all living organisms, and is now known as ‘RNA interference’. What is absolutely fascinating about all this is that certain microRNAs have been associated with certain diseases in humans, such as cancer and others, thus opening the way for the development of new therapies to combat these diseases.
Do you think this prize could encourage more research into microRNA?
The work honoured now dates back to the 2000s and since then enormous advancements have been made in this field. We now know that microRNAs are a special class of non-coding RNAs that exist in eukaryotic organisms (i.e. in animals, plants and other organisms). The developments in this research field have been supported by major funding from big pharmaceutical companies. More than a thousand microRNAs are currently known in humans and there is great hope that we will soon be able to use this knowledge in the field of human health.
Even in prokaryotes, such as bacteria, there are known mechanisms for regulating gene expression based on non-coding RNAs (which are not microRNAs, but whose basic mechanism of action is similar). Knowledge of non-coding RNAs in bacteria could open up new ways of fighting infections, especially those caused by bacteria resistant to multiple antibiotics, which are an increasing problem on a global scale.
On a final note, I’d like to address the issue of funding for applied research to the detriment of so-called basic or fundamental research. Two fundamental works in the field of medicine have been awarded in two consecutive years – this year, the discovery of microRNAs and, in 2023, the work of Katalin Karikó and Drew Weissman on discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19. These are two examples of how fundamental knowledge is absolutely central to finding innovative solutions to completely new and potentially global problems, such as the pandemic of recent years.
Professor Jorge Leitão’s comments in the media:
