MicroRNAs (or miRs), small non-coding RNAs, participate in the regulation of the genome: this discovery was made during the 1990s by the biologist Victor Ambros and the geneticist Gary Ruvkun. The description of this fundamental principle earned them the 2024 Nobel Prize in Medicine or Physiology. Their work, “the repercussions of which we are still experiencing thirty years later”, according to Hervé Seitz, a specialist in miRs at the Institute of Human Genetics in Montpellier, have deconstructed the paradigm stating that gene regulation only occurs through proteins.
In 1993, Victor Ambros demonstrated the negative regulation of one gene (Lin-4) over another (Lin-14) in the model organism Caenorhabditis elegans and observes that Lin-4 produces a small RNA, not translated into protein. Separately, Gary Ruvkun finds that the Lin-14 gene is negatively controlled by a small segment of RNA. The two researchers quickly understood that they had identified the same oligonucleotide: the first microRNA ever described. Today, we know much more: our genome is mainly regulated by miRs, which form very stable ribonucleic complexes, capable of recognizing and regulating messenger RNAs.
This prize is in line with the 2006 Nobel which rewarded Andrew Fire and Craig Mello for their work on another type of non-coding RNA: small interfering RNA (siRNA). “The entire community of researchers working in the field of non-coding RNAs was surprised that Ambros and Ruvkun did not also receive the prize at the time,” remembers Jérôme Cavaillé, researcher at the Center for Integrative Biology in Toulouse.
No medical application has yet been successful, but Ambros and Ruvkun’s discovery opens up perspectives in the development of therapies in cardiovascular, metabolic diseases or cancer. miRs are also considered as diagnostic and prognostic markers.
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