Diving into the heart of a little-known and vital 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 so-called “eukaryotic” organisms, these animals, fungi, plants or yeasts composed of cells with a nucleus.

In the magazine Science from October 31, a Spanish and American team dismantles the fine cogs of this biochemical clockwork. Knowing them also means better understanding a paradox: how, over the course of evolution, have eukaryotes been able to become so complex, even though the number of their genes barely increased?

“A little nematode worm, Caenorhabditis eleganshas 19,000 genes, while our species has barely 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.

By what stratagem? Here we need to return to a basic lesson from life and earth science classes: how are the proteins in our cells produced? During a first step, the DNA sequence of a gene is “transcribed” into a so-called “pre-messenger” RNA molecule, a sort of copy of this DNA sequence. Then, proteins are formed by the translation of the message written in this RNA, thanks to a genetic code.

Alternative epissage

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

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

Over the course of evolution, an even more subtle process, alternative splicing, has been retained by natural selection. This is the possibility, for a pre-messenger RNA from a given gene, to undergo different splicing, leading to different proteins.

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