What triggers RNAi?

The discovery of RNA interference revolutionized the way we determine the role of a gene.  The gene silencing phenomenon has been shown since the early 1990s when introduction of sense or anti-sense RNA could cause a reduction of endogenous messenger RNA.  In 1998, Fire and Mello provided an explanation for the previously reported silencing effect.  Their seminal paper shows that it was not ssRNA that silenced the endogenous RNA, but in fact dsRNA.  So how did ssRNA cause silencing in previous reports?  It is believed that their ssRNA preparations were contaminated with complementary RNA!  Fire and Mello overcame this by extensively purifying their RNA.  Indeed,  they showed that ssRNA was consistently found to be 10 to 100 fold less effective than double stranded.  To this day biologists continue to make great strides in understanding the roles of genes due to this discovery.
Nobel prize article and image credit 

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