Double Strand RNA Interference or RNAi

The Discovery and Extent of RNAi The first hint that double stranded RNA could inhibit gene function was a serendipitous finding by Guo and Kemphues (1995) that injection of sense RNA to a par-1 gene in the gonad of the nematode, C. elegans, induced par-1 null phenocopies at the same high frequency as injection of antisense RNA. The mystery was solved in 1998 by Fire et al. (1998), who showed that injection of dsRNA for specific genes into C. elegans caused a specific disappearance of the gene products from both the somatic cells and the F1 progeny. Injection of single stranded RNA for the genes had little effect. Use of dsRNA unrelated to the specific gene had no effect. They also showed that the effect was on the stability of the mRNA. The dsRNA appeared to cross cellular barriers and could work at a distance from the injection, and only a few molecules of dsRNA per cell were required, suggesting that a catalytic or amplification process was occurring. Only dsRNA sequences from exons had an effect; sequences from introns had no effect. See table of their results below.