The term “simple” is often associated with “ancient” in the field of evolution. Indeed, the more simple an organism, the more we tend to consider it ancient (and vice versa). This excessively limited vision of things has once again been put to the test by researchers in Liège. The latter have discovered that the machinery of the last common eukaryotic ancestor was already highly complex, especially in terms of the RNA maturation process.  

A cell is comparable to a miniature factory. Just like a factory, the cell needs energy and raw materials to function and, thanks to a well-organised production line, it generates finished products as well as waste. The cells’ machinery is essentially programmed to create proteins. While all cells are equipped with this sophisticated machinery, the type of proteins they produce depends on their function.

There are various stages along the protein production line, in particular, transcription, splicing and translation.

During transcription, the DNA double helix unwind to allow the RNA polymerase, an enzymatic complex, to come and read the sequence on the single strand of DNA corresponding to the gene that encodes the protein to be produced. As it moves along the DNA, the RNA polymerase synthesizes a precursor RNA called the pre-mRNA. As well as containing all the information required to generate the said protein, it also includes superfluous information that must be eliminated before the translation of the mRNA into the amino acids composing the protein. “In eukaryotes, the genes are split up or arranged in a patchwork, i.e., they are constituted of coding and regulating sequences, the exons, and non-coding sequences, the introns”, explains Professor Patrick Motte, in charge of the Laboratory of Functional Genomic and Molecular Plant Imaging at ULg. “The exons are the parts you find on the mature mRNA while the introns will be eliminated”, continues Patrick Motte. Thus, the pre-mRNA will undergo a sort of cleaning process during which it will be relieved of its introns and after which it will then be mature and ready to be translated. “The process during which the introns are recognised then eliminated, and the exons are linked to one another, is called splicing”, Patrick Motte elaborates.

Several proteins for a single gene

Up until recently, it was commonly agreed that a gene encodes a specific protein through the intermediary of a mature mRNA that is generated after the constitutive splicing of a pre-mRNA. Constitutive splicing means that every intron is eliminated and every exon is retained in the final mRNA. This traditional set-up was completely turned upside down several years ago by the discovery of another type of splicing: alternative splicing. Contrary to constitutive splicing, this second form of splicing doesn't strictly result in the exclusion of all the introns and the inclusion of all the exons in the mature mRNA. Depending on various as yet unknown events, during alternative splicing, some exons may not be retained and some introns may be included in the mature mRNA. Hence, the expression of a gene may lead to the formation of several different mRNA and therefore the production of several different proteins, or protein isoforms.