Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.

The authors reported that tiny snippets of double-stranded RNA (dsRNA) effectively shut down specific genes, driving the destruction of messenger RNA (mRNA) with sequences matching the dsRNA. As a result, the mRNA cannot be translated into protein. Fire and Mello found that dsRNA was much more effective in gene silencing than the previously described method of RNA interference (RNAi) with single-stranded RNA. Because only small numbers of dsRNA molecules were required for the observed effect, Fire and Mello proposed that a catalytic process was involved. This hypothesis was confirmed by subsequent research.
Order of authorship in the original publication: Fire, XU....Mello.  

In 2006 Fire and Mello shared the Nobel Prize in Physiology or Medicine for "for their discovery of RNA interference - gene silencing by double-stranded RNA."