nobel medicina 2024 microRNA

What is microRNA, the discovery that won the 2024 Nobel Prize for Medicine for Ambros and Ruvkun

Source: www.nobelprize.org

The Nobel Prize for Physiology or Medicine 2024 it went to the Americans Victor Ambros And Gary Ruvkumboth molecular biologists at MIT in California, for discovering in 1993 The microRNA (small specific RNA sequences involved in gene expression) and its function, which until some time ago had only been hypothesized, linked togene expression and mRNA maturation. MicroRNA is in fact crucial for the regulation of genes, cellular differentiation and in general for the correct functioning of multicellular organisms, including humans. The honor also indirectly recognizes the importance that RNA (the nucleic acid mainly involved in the synthesis of proteins) is having in recent years: just think of the vaccines for COVID-19 or the new anti-tumor vaccines, based on new discoveries regarding RNA.

What are microRNAs and what are they for

THE microRNA they are small RNA molecules, a single strandconsisting of 21 to a maximum of 25 nucleotides (i.e. the fundamental units of RNA) and are part of the so-called “short interfering RNAs“. Generally RNA is involved in the synthesis of proteins, but microRNAs do not have this function: they instead serve to regulate gene expression. In this case, the function of the microRNA is to ensure that some parts of themRNA (the messenger RNA, which is used to produce proteins and therefore to actively express what is written in the genes) are not translated into proteins. Simply put, microRNA prevents the formation of certain proteins in the cell.

This is very useful, because allows specific differentiation of cells. Our genetic code is present in all our cells, but these are still very different from each other: for example, a muscle cell is very different from a neuron and therefore will have to express the same genes in a different way. MicroRNAs are crucial in ensuring that only the correct set of genes are active in each specific cell type, specializing it And differentiating it. In this way, each cell can carry out its own task specialized function.

Why the discovery of microRNAs is important

Ambros and Ruvkum published the microRNA discovery in two journal articles Cell in 1993, in which they exposed the results of their experiments on C. elegansa nematode (a kind of worm) about 1 millimeter long. Individually, the two researchers had analyzed two particular mutations of this worm, one that made the worm longer than normal (mutation on the gene called lin-4studied by Ambros), and the other which made the worm shorter than normal (mutation on the gene called lin-14studied by Ruvkun). Conducting similar experiments, the two researchers decided to evaluate the situation togetherexchanging information and joining forces. From this union was born the discovery that would lead to the Nobel: the two scientists demonstrated that lin-4 was a microRNA that “turns off” lin-14, blocking the production of the lin-14 protein.

For years it was thought that this discovery was peculiar to that type of organism, but today we know that gene regulation by microRNAs is universal among multicellular organismsand it also happens in our species. Us Homo sapiens we have hundreds of microRNAs with specific functions.

This discovery is surprising because it allowed us to understand one of the principles that regulates sophisticated gene activity: these microRNAs allow cells to select useful instructions and deactivate those that are not useful to itself and its specialization.
Therefore, this is a discovery of fundamental importance for understanding the mechanisms that lead to differentiation of a cellwhich becomes a specific cell instead of another.

microRNA gene expression
Diagram of the role of microRNA in gene expression. Credit: The Nobel Committee for Physiology or Medicine. III. Mattias Karlén

The possible applications of microRNAs in medicine

MicroRNAs have a enormous relevance at a pathological and physiological level. Their anomalous regulation, their mutation or absence can lead to various forms of cancera disorders congenital to the ear, eyes and skeleton, as well as to illnesses cardiac or nervous system, diabetes and damage to various organs.

A striking example of a pathology in which microRNAs play a key role is the DICER1 syndromea very rare hereditary disorder in which the individual develops a very strong propensity to have tumors in several organs, including the kidney, lung, brain, testicles, thyroid, ovary, cervix and eyes, especially during childhood. Well, this syndrome originates from a mutation on specific microRNA genes.

Another reason for the importance of microRNAs is that they can also influence the regulation of the expression of genes other cells surroundings. MicroRNAs, in fact, can be transported through biological fluids once secreted by the cells that produced them, acting in the target cells of other body areas, exerting the action of suppression, specialization and differentiation in that new cell. As they travel in body fluids, these microRNAs are stabilized And protected by other molecules, which do not allow immediate degradation.

By being researchers able to synthesize microRNA in the laboratorya promising line of research involves using these molecules to silence genes that underlie many diseases or syndromes. Besides, they could be the basis for newly developed drugs.