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Diving into the heart of a vital and little-known cellular machinery, the human spliceosome

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Diving into the heart of a vital and little-known cellular machinery, the human spliceosome

The spliceosome. Under this abstruse name hides a crucial piece of machinery for the proper functioning of our cells. Its mission: to participate in the control of the activity of our genes, like those of all organisms called “eukaryotes”, whether animals, fungi, plants or yeast, composed of cells with a nucleus.

in the magazine Science Starting October 31, a Spanish and American team dismantles the fine gears of this biochemical mechanism. Knowing them also means better understanding a paradox: how, throughout evolution, have eukaryotes been able to become so complex, even though the number of their genes has barely increased?

“A small nematode worm, Caenorhabditis elegans“It has 19,000 genes, while our species barely has more.”underlines Clément Charenton, researcher at the Institute of Genetics and Molecular and Cellular Biology (CNRS), in Strasbourg. So, we have 22,000 protein-coding genes; However, our cells can produce more than 200,000 different proteins.

Also read (2022) | Article reserved for our subscribers. Sequencing of the human genome is (almost) coming to an end

With what stratagem? Here we must return to a basic lesson from life and earth science classes: how are proteins made in our cells? In a first stage, the DNA sequence of a gene is “transcribed” into an RNA molecule called “premessenger”, a kind of copy of this DNA sequence. Proteins are then formed by translating the message written in this RNA, thanks to a genetic code.

Alternative splicing

It is between these two stages where the spliceosome operates. One of the keys to the matter is hidden in the structure of genes: these, in most cases, are sequences of so-called “coding” DNA sequences, exons and so-called sequences. non-coding”, introns. And the premessenger RNA molecule is complementary to both exons and introns.

But then a strange phenomenon occurs: the RNA sequences corresponding to the introns are cut and removed. Only the RNA sequences corresponding to the exons, once joined, will give the messenger RNA, which will be translated into proteins. This process is called “splicing.” Its discovery in 1977 earned the British Richard Roberts the Nobel Prize in Physiology or Medicine and the American Phillip Sharp in 1993.

Throughout evolution, natural selection has retained an even more subtle process, alternative splicing. This is the possibility that a premessenger RNA from a given gene undergoes different splicing, resulting in different proteins.

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