Two American scientists, Victor Ambros and Gary Ruvkun, share this year’s Nobel Prize in Medicine for the discovery of “microRNA and its role in the post-transcriptional regulation of gene expression”, according to the official announcement of committee of the prestigious award which took place today shortly after noon.
But what does this discovery mean and why was it deemed worthy of the highest scientific honor? It is important to recall here that although it has prevailed to call the prize the “Nobel of Medicine”, the full title of the prize is “Nobel of Medicine or Physiology” and it would be correct to say that this year’s two laureates receive the Nobel of Physiology as they discovered a mechanism absolutely necessary for life.
Information flow
But let’s start from the beginning: the human body consists of trillions of cells, and each of them has the same DNA. That is, the same genetic material, the same recipe for the creation of each of us which resulted from the fusion of our mother’s egg and our father’s sperm. Despite the fact that cells have all the genetic information, they only use what they need according to their function. For example, other genes need to activate muscle tissue cells in order for us to walk and use our hands and other cells inside the gut to properly absorb food. Regardless of the gene, however, the flow of information in a cell is common: the information for the synthesis of a protein (for example, hemoglobin so we can breathe, or myosin so we have functional muscles) is based in the DNA, but is not utilized in the cell nucleus where the DNA is located. There, the section of DNA that corresponds to a desired protein is transcribed into mRNA (messenger RNA) which leaves the nucleus and is directed to the points where its translation into the specific protein takes place.
Critical issue
How, out of the more than 20,000 genes present in the human genetic material, each cell utilizes only those it needs for the synthesis of its proteins has been one of the most basic problems of biology. And the truth is that for a while at the end of the 20th century it was thought that the problem had been solved as a number of transcription factors (proteinaceous molecules that bind to DNA and trigger transcription) had been discovered. Thanks to the work of this year’s two awardees, however, it turned out that the solution was not complete!
From the lab animals…
Both worked with the laboratory animal Caenorhabditis elegans, a tiny worm (a millimeter-long nematode) composed of about 1,000 specialized cells. In other words, this experimental animal has a nervous, digestive and reproductive system with their corresponding cells. Ambros and Rafkan studied two strains of C. elegans, lin-4 and lin-14. The first stem was longer than normal and the second much shorter. Such changes occur when the expression of specific genes is deregulated, and the two then young postdoctoral students decided to look for the molecular mechanisms that would explain this difference in the length of the experimental animals compared to the normal strains.
…down to human
Initially, in 1993, Ambros noticed that the lin-4 gene did not lead to the creation of a protein, but of a small RNA molecule (microRNA). In collaboration with Rafkan, they found that this tiny RNA put the brakes on the synthesis of the lin-14 protein, which is essential for the animal to attain normal length. In other words, they found that lin-4 acted as a protein translation control factor, something that had never been observed before. How surprising this finding was, (that is, an RNA molecule having a regulatory role in protein synthesis and an extremely tiny one at that), is also shown by the fact that it was initially thought to be a peculiarity of C. elegans. But today we know that in the human body there are at least 1000 different functional microRNAs which control which proteins will be synthesized and when.
The importance of discovery
This is why Ambros and Rafkan’s discovery was deemed so important as to deserve a Nobel: because they have revealed yet another safety valve that allows the healthy development and functioning of organisms, including humans.
We are used to Nobel Prize announcements being accompanied by their applications. At the moment there is no such application, such as for example a drug based on the findings of Ambros and Rafkan. But this does not diminish the value of their discovery. On the contrary! Understanding the molecular mechanisms that govern cell function, i.e. understanding how life works is the first and fundamental step for any future application.
