<P> The process of RNAi was referred to as "co-suppression" and "quelling" when observed prior to the knowledge of an RNA - related mechanism . The discovery of RNAi was preceded first by observations of transcriptional inhibition by antisense RNA expressed in transgenic plants, and more directly by reports of unexpected outcomes in experiments performed by plant scientists in the United States and the Netherlands in the early 1990s . In an attempt to alter flower colors in petunias, researchers introduced additional copies of a gene encoding chalcone synthase, a key enzyme for flower pigmentation into petunia plants of normally pink or violet flower color . The overexpressed gene was expected to result in darker flowers, but instead caused some flowers to have less visible purple pigment, sometimes in variegated patterns, indicating that the activity of chalcone synthase had been substantially decreased or became suppressed in a context - specific manner . This would later be explained as the result of the transgene being inserted adjacent to promoters in the opposite direction in various positions throughout the genomes of some transformants, thus leading to expression of antisense transcripts and gene silencing when these promoters are active . Another early observation of RNAi was came from a study of the fungus Neurospora crassa, although it was not immediately recognized as related . Further investigation of the phenomenon in plants indicated that the downregulation was due to post-transcriptional inhibition of gene expression via an increased rate of mRNA degradation . This phenomenon was called co-suppression of gene expression, but the molecular mechanism remained unknown . </P> <P> Not long after, plant virologists working on improving plant resistance to viral diseases observed a similar unexpected phenomenon . While it was known that plants expressing virus - specific proteins showed enhanced tolerance or resistance to viral infection, it was not expected that plants carrying only short, non-coding regions of viral RNA sequences would show similar levels of protection . Researchers believed that viral RNA produced by transgenes could also inhibit viral replication . The reverse experiment, in which short sequences of plant genes were introduced into viruses, showed that the targeted gene was suppressed in an infected plant . This phenomenon was labeled "virus - induced gene silencing" (VIGS), and the set of such phenomena were collectively called post transcriptional gene silencing . </P> <P> After these initial observations in plants, laboratories searched for this phenomenon in other organisms . Craig C. Mello and Andrew Fire's 1998 Nature paper reported a potent gene silencing effect after injecting double stranded RNA into C. elegans . In investigating the regulation of muscle protein production, they observed that neither mRNA nor antisense RNA injections had an effect on protein production, but double - stranded RNA successfully silenced the targeted gene . As a result of this work, they coined the term RNAi . This discovery represented the first identification of the causative agent for the phenomenon . Fire and Mello were awarded the 2006 Nobel Prize in Physiology or Medicine . </P>

Rnai is initiated by which leads to the of specific genes