Nobel Prize in Medicine: microRNAs, key cogs in a tremendously complex genome

What is a microRNA?

These are bits of ribonucleic acid (RNA). Present in all our cells, RNA is synthesized by our body from genes gathered in our DNA.

MicroRNAs do not play the best-known role of RNA, that of intermediary between our genes and the production of the myriad proteins that make our body function, for which we speak of messenger RNA.

MicroRNAs are part of so-called “non-coding” RNA: they are not translated into proteins.

But that doesn’t mean they don’t play a role. The discovery of microRNAs in the 1990s by Victor Ambros and Gary Ruvkun, both Nobel Prize winners on Monday, showed that our genome was not a simple straight line between DNA, RNA and then proteins.

“The discovery of microRNAs has brought an additional level of complexity by revealing that regions previously thought to be non-coding play a role in gene regulation.“, explains Benoît Ballester, researcher at Inserm and specialist in non-coding genomes, to AFP.

These microRNAs interfere with the functioning of messenger RNA: “It’s like Velcro that attaches to it and prevents it from being translated into proteins.“, says Mr. Ballester.

Consequence: certain genes are expressed little or not at all – they are inhibited -, and others more markedly – they are intensified.

However, we should not imagine microRNAs as a form of internal parasites that would spoil the proper functioning of our genome.

They form “an integral part of the regulation of our genome, it is as important as the classic translation of a gene into protein“, underlines the non-coding genome specialist.

Why is this so interesting?

The discovery in 1993 of the first microRNA by Victor Ambros was not immediately hailed as a major breakthrough.

The researcher was a specialist in the biology of certain worms, and it was in one of them (a one-millimeter round worm, called C. elegans) that he identified the existence of micro-RNA.

“Nobody really paid attention“, admits to AFP Eric Miska, geneticist at the University of Cambridge, admitting that it took years to see something else.”something weird about worms“.

It was in 2000 that Gary Ruvkun identified the existence of similar mechanisms in humans, opening the way to a whole new area of ​​genomics.

“This tiny piece of RNA, so important for the development of this little worm, we also have it, you and I“, underlines Eric Miska. “And it even plays an essential role, since it prevents the appearance of tumors“.

What concrete benefits?

If knowledge of microRNAs already allows us to understand our genome much better, it remains to be seen whether they can serve as a lever for action to cure diseases. For several years, a number of biotechnology companies have been banking on this avenue.

It is particularly a promising area against cancers, with the idea of ​​establishing highly targeted treatments. This research is part of a broader context where we understand better and better how tumors can develop differently at the molecular level from one patient to another.

However, against cancer or other pathologies, there is still “nothing that is close to a real application“, Gunilla Karlsson Hedestam, professor at the Karolinska Institute, told the press during the Nobel Prize announcement in Stockholm.

MicroRNAs are indeed a complex target to manage due to their instability.

But, without necessarily making them the basis of a drug, many researchers first hope to use them as a “biomarker”, that is to say a diagnostic tool which would make it possible, for example, to identify which type of cancer the patient is confronted.