chapter  46
4 Pages

RNA Interference

The use of transgenic plants led to the discovery in the early 1990s of unsuspected (and so far unexplained) mechanisms of silencing of gene expression. In fact, this non-expression was observed during the construction of a transgene that was supposed to overexpress the target gene. How can a desired overexpression result in the silencing of expression of the transgene and the homologous copy of the gene already present in the cell? Or, more trivially, how can 1 + 1 = 0? The artificial input of supplementary copies into the cell seems to block any expression of different copies of this gene. It was subsequently demonstrated that these phenomena occur at the post-transcription level and result from the specific degradation of homologous messenger RNA coming from the endogenous gene and the transgene. The study of these phenomena, called post-transcriptional gene silencing (PTGS), has demonstrated the amplification of double-stranded RNAs (dsRNAs). Their formation results, depending on the case, from the presence of reverse repetitions at the transgenic locus leading to the transcription of sense-antisense mRNAs, or the high production of "sense" transcripts by a mechanism that remains unexplained. Moreover, in 1998, it was demonstrated in the nematode Caenorhabditis elegans that the injection of dsRNA induced the inactivation of homologous endogenous genes. This phenomenon, named RNA interference (or RNAi), very quickly showed great similarities with PTGS: (1) intervention of dsRNA in the inactivation of gene expression; (2) similarity between several proteins controlling the phenomena, (3) accumulation of small RNAs of 21 to 25 sense or anti-sense nucleotides homologous to the mRNA of the inactivated gene; and (4) propagation of an inactivation signal that, from a localized initiation, will sometimes induce the inactivation in the entire organism by a systemic response.